[A retrospective analysis of using zonisamide and retention in monotherapy among patients with epilepsy in routine clinical practice]. / Retrospektivnyi analiz primeneniia i uderzhaniia na monoterapii zonisamidom bol'nykh épilepsiei v usloviiakh povsednevnoi klinicheskoi praktiki.

INTRODUCTION: Zonisamide is one of the first antiepileptic drugs of new generation with a wide spectrum of action. It is successfully used in treatment of epilepsy for 30 years. The study aims at analyzing the results of the multicenter Russian trial on the efficacy and tolerability of zonisamide and retention in monotherapy. MATERIAL AND METHODS: The analysis included 92 patients with focal epilepsy, aged 18-78 years, from 20 epileptology centers in different regions of Russia. The patients were treated with zonisamide in initial and subsequent treatment. RESULTS AND CONCLUSION: The efficacy (the reduction of seizure frequency by >50%) was achieved in 81 (91%) out of 89 patients (95% CI 83.6-95.7%). Fifty-two patients received zonisamide for more than one year. The efficacy was achieved in 50 (96.2%) (95% CI 88.2-99.2%), including 39 (79.6%) patients with remission out of 49 patients with assessment of seizure free periods (95% CI was 66.8-89% for the frequency of remissions). The adverse effects were recorded in 27 (29.3%) patients. Seven (7.6%) patients were withdrawn due to these effects. The maximal duration of observation period was 50 month. Mean time of retention in treatment was 42.4 month (95% CI 38.7-46.2 month). The total frequency of retention in treatment was 82.1% (95% CI 73.1-91%) during the whole observation period.

[Brivaracetam in the treatment of patients with epilepsy]. / Brivaratsetam v lechenii bol'nykh épilepsiei.

The newest antiepileptic drug (AED) brivaracetam (Briviac, UCB Pharma) (BRV) was approved in the Russian Federation in 2017 as an adjuvant therapy for the treatment of partial seizures with/without secondary generalization in adults and adolescents over 16 years old with epilepsy. This review contains the data of BRV preclinical studies, pharmacokinetic profile and the results of comparative study of BRV and LEV. The results of main studies of efficacy and tolerability with pooled analysis as well as data from meta-analysis are presented. The authors present conclusions of the Russian leading epileptologists on perspectives of using BRV in different populations of epileptic patients. The use of BRV is able to provide long-term efficacy in terms of seizure control, is well tolerated, keeps quality of life and social activity of people with epilepsy.

[Lacosamide (vimpat). Prospects for clinical application]. / Lakosamid (vimpat). Perspektivy klinicheskogo primeneniia.

This article presents the review of the most significant studies of the efficacy and tolerability of lacosamide (LCM) in treatment of patients with focal epilepsy. The review includes the results of the main studies which preceded the official approval of LCM use in mono- and polytherapy. Results on the efficacy of LCM in long-term use and treatment retention in clinical practice, most effective LCM combinations, tolerability, an influence on cognitive and mental functions, advantages in treatment of elderly patients are presented. Characteristics of LCM in comparison with other sodium channel-blocking antiepileptic drugs and selection priorities are shown. The authors assess perspectives of further use of LCM in clinical practice.

[Diabetic asymmetric proximal neuropathy]. / Diabeticheskaia asimmetrichnaia proksimal'naia neiropatiia.

AIM: To study the prevalence, clinical features and treatment of diabetic asymmetric proximal neuropathy (DAPN). MATERIAL AND METHODS: Four hundred and forty-five patients with diabetes mellitus (DM), 257 women and 188 men, mean age 47.6±0.5 years, including 163 patients with DM type I and 282 with DM type II, were examined. RESULTS AND CONCLUSION: Distal symmetric sensory motor polyneuropathy was found in 62% of the patients, autonomic neuropathy in 25.6%, somatic mononeuropathy in 28.5%, DAPN in 7.9%. DAPN was more frequent in patients with DM type II (9.6), with poor control of glycemia and DM duration more than 5 years. Pain and paresthesia in a zone of innervation of several roots and nerves, amyotrophy that spread beyond the definite myotome were key symptoms of DAPN. The efficacy of double therapy of neuropathic pain (pregabalin and duloxetine) and vitamin B complex was shown. A role of glucocorticoids and normal human immunoglobulin in treatment of DAPN is discussed.

[New possibilities of monotherapy of symptomatic and cryptogenic partial epilepsy].

This literature review is devoted to the use of the antiepileptic drug zonisamide in the initial monotherapy of symptomatic and cryptogenic partial epilepsy. The review is based on the results of the trials, level of evidence A, that demonstrate the efficacy and tolerability of zonisamide comparable to those of carbamazepine. The possible advantages of zonisamide in different clinical situations and characteristics of its use related to molecule structure, pharmacokinetics, mechanisms of drug action are discussed.

[Acute symptomatic epileptic seizures and status epilepticus].

Acute symptomatic seizures (ASS) are the seizures of different etiology that occur in close temporary relationship to acute damage of the central nervous system arising simultaneously due to metabolic, toxic, infectious and inflammatory factors and structural brain damage. At the time of its origin, ASS is often not distinguished from epileptic seizures in the clinical and electrophysiological parameters, although represent a fundamentally different state from the point of view of pathogenesis, therapy and prognosis. Tactics in the ASS and symptomatic epileptic status of any nature provides for the immediate carrying out differential diagnosis and differential treatment. Treatment of ASS includes two aspects: reduction in ictal activity (seizures) and prevention of future development of seizures through the elimination or correction of physiological trigger of the attacks and the decision to conduct a long-term antiepileptic drug therapy if the risk of seizures is saved.

[Possibilities of using intravenous forms of antiepileptic drugs in epileptic seizures]. / Vozmozhnosti primeneniia vnutrivennykh form protivoépilepticheskikh preparatov pri épilepticheskikh pristupakh.

The literature data on using intravenous forms of AEDs that expand treatment possibilities for patients with epilepsy are presented. AEDs can be used in different situations, when patients are not able to take AEDs in per os. These situations can include seizure emergencies (recurrent seizures, clusters, status epilepticus), caused by disease decompensation; acute symptomatic seizures; perioperative preparation in the case of surgery; dysphagia; gastrointestinal problems; psychiatric disorders, and others. This article is based on a review of International and Russian expert consensus practice guidelines for management of clinical situations mentioned above. The authors present data on available Russian parenteral forms of drugs used today (valproats, levetiracetam, lacosamide, diazepam, midazolam, propofol, thiopental potassium). It has been concluded that an ideal intravenous AED should be highly effective, acts fast, has no severe adverse effects, has low drug-drug interactions, does not require frequent plasma concentration monitoring, and should be easily switched to a per os form without any additional titration. The importance of separate treatment approaches on different stages of medical help is emphasized. The choice of drug used can be influenced by a particular clinical situation, indications/contraindications, the recommended infusion speed, side effects, possible drug-drug interactions with other AEDs and other drugs used for the treatment of concomitant diseases, availability of a particular drug at the moment and the level of a physician's knowledge of usage of intravenous forms of AEDs.

[Pharmacotherapy of epilepsy: the use of topiramate in initial and additional treatment].

Topiramate (topamax) is an antiepileptic drug of the new generation that was first registered and introduced in clinical practice in 1995. Due to its effective clinical properties, the drug is used widely all over the world including Russia where it has been using since 1999. Topamax is a principally new antiepileptic drug (AED) with the unique mechanism of action, favorable pharmacokinetics, high efficacy and safety. During its existence, it is widely accepted as an AED of first choice for additional and initial treatment of many forms of epilepsy in children over 2 years old and adults including old patients of both sexes. The drug can be successfully used as monotherapy and as well as polytherapy in treatment of most severe and "catastrophic" epilepsies resistant to any previous treatment.

[Epilepsy in elderly].

Seventy-two elderly patients with a possible diagnosis of epilepsy were studied. A study included the evaluation of anamnesis, clinical and neurological examination, EEG and/or video-EEG-monitoring, MRI of the brain. The follow-up period was 1-5 years (on average 3 years). Epilepsy was confirmed in 58 cases. Symptomatic partial epilepsy was diagnosed in 43,1% patients, cryptogenic - in 55,2%. Cerebrovascular accidents were the most frequent cause of symptomatic epilepsy. The distinct feature of the cohort studied was the non-compliance recorded in a half of all patients. In the end of the study, 46,6% patients received carbamazepine, 34,5% - valproate, 24,1% - phenobarbital, 13,8% - topiramate, 3,4% - phenytoin, 1,7% - lamotrigine and 12,1% of patients did not use antiepileptic drugs. Clinical features, efficacy of diagnosis and treatment as well as reasons of non-compliance in elderly epileptic patients were described and analyzed.

[Topiramate as an example of using generics in the treatment of epilepsy].

Causes of losing the pharmacological remission with duration of more than one year have been analyzed in 220 patients with epilepsy. The most often cause of losing control of seizures was switching from brand antiepileptic drugs to generic analogue (60,4% of patients) with 28,2% of them being switched to topiramate generics. The results of switching of 160 patients from the brand form of topiramate (topamax) to its generics were compared to those in the control group of 52 patients who continued to receive the original form. As a result of switching the remission was lost in 75,6% of patients, epileptic status in 3,75%; 51,9% of patients needed emergency care and hospitalization. Switching back to original medication was done in 86,2% of patients with the following increasing of initial doses of topamax in 58,0% and transition from mono- to polytherapy in 60,0%. The baseline level of seizure control has been achieved only in 32,9% of patients.

[Levetiracetam (keppra) in the treatment of different epileptic syndromes in adults].

One hundred and thirty-eight patients (76 women and 62 men, aged from 16 to 65 years) with symptomatic partial epilepsy (n=128) and idiopathic generalized epilepsy (n=10) have been studied. All patients received keppra on regiments of monotherapy (n=30) and polytherapy (n=108). The study included evaluation of anamnesis, clinical and neurophysiological examination, routine EEG and/or video-EEG-monitoring, MRI of the brain, assessment of effectiveness, tolerability and quality of life (QUALIE-31, version 1). The period of observation was 1-4 years (on average 2,5 years). The high effectiveness and tolerability, good characteristics of therapy duration, the early appearance of clinical effect after the therapy has been started and positive cognitive effect are noted. The effectiveness, tolerance and clinical features of keppra treatment in different epileptic syndromes are analyzed.

[Initial precipitating injury and symptomatic focal epilepsies].

A study included 793 epileptic patients. Symptomatic epilepsy caused by initial precipitating injury (IPI) was diagnosed in 151 cases. Evaluation of anamnesis, clinical and neurological examination, routine EEG and/or video-EEG-monitoring and MRI of the brain were carried out. Period of observation was 6 months - 5 years (on average 3 years). Age of IPI was reversely correlated with duration of latent period (LP). High frequency of seizures was correlated with poor effectiveness of treatment. Different types of IPI differed by frequency of seizures, duration of LP and effectiveness of treatment.

[Occipital lobe epilepsy in adults].

Five hundreds and thirty-six patients, aged from 19 to 50 years, have been studied. Occipital lobe epilepsy (OLE) have been diagnosed in 22 (4,1%) of cases. The study included evaluation of anamnesis, clinical and neurological examination, routine EEG and/or video-EEG monitoring and MRI of the brain. Duration of the study was 1-5 years (on average 3 years). The most typical clinical features were visual phenomena, mostly "irritation symptoms" represented by elementary hallucinations. Visual "symptoms of loss" (scotomas, amaurosis) are associated with ineffectiveness of antiepileptic drugs. The regional epileptiform activity in occipital leads is found in the routine EEG in 1/4 of patients, epileptogenic structural lesions of the same localization in the MRI - in 1/3 of patients. The data suggest that these diagnostic methods are not sufficient and support the validity of clinical diagnosis.

[Non-terminal remission in epileptic patients].

Seven hundreds and fifty-eight patients with epilepsy have been studied. Non-terminal remission (temporal stop of seizures with the following relapse) has been diagnosed in 18,3% of cases. An aim of the study was to investigate clinical characteristics and prognosis in patients with such type of remission. The study included evaluation of anamnesis, clinical and neurological examination, routine EEG and/or video-EEG-monitoring, MRI of the brain. The period of observation was 1-5 years (on average 2,5 years). As a result, patients were diagnosed with idiopathic generalized epilepsy (18 cases), epilepsy with rare, usually secondary generalized, seizures (37 cases), drug-induced remission (46 cases) and long-term spontaneous remission usually associated with late childhood and adolescence (18 cases). These groups differed by clinical features and effectiveness of antiepileptic therapy. In conclusion, patients with non-terminal remission represent a heterogeneous group with different character of epileptic syndromes, forms of disease and prognosis.

[Clinical and economical effectiveness of the treatment of focal epilepsies].

One hundred and seventy-three patients with symptomatic and probable symptomatic epilepsies, mean age 31.2 years, were studied. The study included evaluation of anamnesis, clinical and neurological examination, routine EEG and/or video-EEG-monitoring, X-ray CT and/or MRI of the brain. The antiepileptic therapy was corrected. The duration of follow-up study was 2 years. General neurologist therapy (initial therapy) and epileptologist therapy (final therapy) were compared using cost-effectiveness analysis, frequency of using different drugs, ABC- and VEN-analysis. The final therapy was effective in 93.1% of cases, a remission was achieved in 53.2%. The ineffective therapy decreased from 56.6 to 6.9%. The ineffective expenses for the initial therapy were 82.8%. The final therapy was significantly effective (p = 0.001) and expensive (p = 0.004) but the cost difference was low (3420 roubles/year).

[Impact of the current antiepileptic drugs on quality of life of epileptic patients].

The purpose of the study was the comparative evaluation of antiepileptic drugs (AED) impact on quality of life (QOL). One hundred and ninety-two patients with symptomatic and probably symptomatic focal epilepsies (mean age 30, 6 +/- 1.05) were investigated. All patients received the following AED as monotherapy: valproate (52), carbamazepine (36), topiramate (56), levitiracetam (24), oxcarbazepine (24). The clinical and neurological examination, EEG and/or video-EEG-monitoring, CT and/ or MRA scan, neuropsychological tests (31-item Quality of Life in Epilepsy--QOLIE-31, version 1 and HUDS) were performed after 3 months of treatment. The higher results of QOL assessment were obtained in the LEV and OXC groups (83.3 and 72%, respectively), the lowest ones--in the CBZ and VPA groups (16.5 and 17%). Clinically relevant emotional disorders occurred more frequently in patients receiving TPM (21.8%), VPA (21.4%) and CBZ (16.6%), significantly rarely in the OXC (8.3%) group and were absent in the LEV group. The strong correlations between QOL, effectiveness, adverse effects and psycho-emotional disorders of AED treatment were found. The best QOL scores were observed in patients treated with newer AED.

[Focal epilepsies in adults: prognosis of treatment effectiveness].

One hundred and seventy-five patients (73 men and 102 women, aged 16-76 years) with symptomatic and probable symptomatic epilepsies, were studied. The duration of disease was from few months to 38 years. The study included evaluation of anamnesis, clinical and neurological examination, routine EEG and/or video-EEG-monitoring, X-ray CT and/or MRI of the brain. The antiepileptic therapy was started or corrected. The period of observation was 1-3,5 years, on average 2 years. Duration of disease, correctness and effectiveness of the previous AED therapy, EEG and neuroimaging data, frequency and type of epileptic seizures were evaluated. A remission was achieved in 96 (54.8%) cases, a reduction of seizures frequency by 50% and more--in 45 (25.8%), no effect--in 34 (19.4%). Epileptiform activity on routine EEG, long disease duration, high frequency of seizures, focal seizures with/without secondary generalization were associated with ineffectiveness of the treatment. Neuroimaging findings and a character of the previous therapy did not impact on the prognosis of disease.