LECTURES
With the development of current neuroimaging techniques, their role in diagnosing epilepsy is becoming more significant and that is not only in identifying the disease that plays a key role in epileptogenesis, but also in assisting a clinician in the subsequent formulation of the diagnosis, in correcting drug therapy, and, in some cases, in addressing the issue of surgical treatment in the patient. The priority technique in this case is magnetic resonance imaging (MRI) that has high sensitivity and specificity in defining the location of minor and more major lesions of the brain structure and that includes a set of current sequences that can obtain important diagnostic information about the functional state of the brain. This article highlights the International League Against Epilepsy guidelines for MRI in patients with suspected epilepsy, assesses the use of and briefly characterizes both structural and functional pulse sequences that are most commonly included in the epileptological protocol. It considers major pathological processes and evaluates anatomical and functional changes in the brain structure, which play an important role in epileptogenesis.
ORIGINAL INVESTIGATIONS
Objective: to comparatively evaluate the clinical efficacy and tolerability of monotherapy with levetiracetam (LEV), a brand-name drug (bLEV; Keppra, UCB Pharma, Belgium) and its generic (gLEV; Epiterra, TEVA, Israel) in adolescent (over 16 years of age) and adult patients with focal epilepsy (FE) during a one-year follow-up period.
Patients and methods. The patients were divided into two groups: 1) bLEV (n = 143) and 2) gLEV (n = 63). Group 2 received monotherapy with gLEV at baseline, or was switched to it from another drug within the international nonproprietary name, or to LEV from monotherapy with another antiepileptic drug (AED) due to inefficiency and/or poor tolerability. The median doses of bLEV and gLEV were 1000 and 1500 mg/day, respectively.
Results and discussion. The results of the clinical trial suggest that LEV shows high efficacy and excellent tolerance in FE therapy. The clinical efficacy of bLEV and gLEV at 12-month follow-up was high and amounted to 82.5% for the two dosage forms. The frequency of adverse events was 17.5% for both bLEV and gLEV. The median dose of LEV was 1000 mg/day for Group 1 and 1500 mg/day for Group 2. Higher LEV doses in Group 2 patients were probably due to their longer disease duration. All patients taking LEV had an excellent or good quality of life and, when switched from other AEDs, showed even an improvement. The comparability of clinical results suggests that there may be bLEV to gLEV and gLEV to bLEV switches, especially during forced drug supply disruptions; however, this substitution should be done only after mandatorily discussing this matter with the patient and telling him about all possible consequences of this substitution.
A relationship of epilepsy and a used antiepileptic drug (AED) with the menstrual cycle, overweight, and reproductive disorders in women has been studied in recent years. In this connection, topiramate engages attention as one of the AEDs that contribute to weight loss, but not gain.
Objective: to investigate the efficacy/tolerability of topiramate in reproductive-aged women with menstrual disorders.
Patients and methods. An analysis was made in a group of 58 patients of fertile age (18–35 years) with a long history of focal epilepsy (FE) (n = 44) or idiopathic generalized epilepsy (IGE) (n = 14) who received mainly combined therapy with 2 AEDs. Different degrees of overweight was observed in 82.8% of the patients; 51.7% had one or another menstrual cycle disorders; however, the women had been followed up by a gynecologist in exceptional cases. Switching from one of the parent AEDs to topiramate or its incorporation into a treatment regimen as an additional drug substantially improved the course of the disease: remission at 12 months was achieved in 59.1% of the patients with FE and in 78.6% of those with IGE.
Results. 29.3% of the patients receiving dual therapy, the second medication of which was topiramate, were noted to have lost weight not only if those had a high baseline body mass index (BMI), but also if those had normal BMI at baseline. 8.6% of all the patients and 16.7% of those with menstrual cycle disorder achieved normalization of menstrual function. Topiramate was discontinued only in 1 (1.7%) patient because of critical weight loss (BMI<15).
Discussion. The use of topiramate that has a wide spectrum of action in different types of seizures and forms of epilepsy in patients with a long history of the disease could achieve seizure remission in 59.1% of the patients with FE and in 78.6% of those with IGE for a period of more than 12 months. One-third of all the cases were observed to have lost 3–13 kg (median, 6 kg) of weight during monotherapy or dual therapy with topiramate. The latter resulted in the normalization of menstrual function in 5 patients, which was 8.6% of all the patients and 16.7% of those with menstrual cycle problems.
Conclusion. In addition to a significant improvement in the disease course, the use of topiramate in monotherapy or dual therapy for FE or IGE can contribute to the normalization of body weight and the menstrual cycle. The authors draw the attention of epileptologists to the need to monitor menstrual function in women with epilepsy.
Objective: to study the gender features of sexuality as one of the structural central ego functions in patients with epilepsy.
Patients and methods. The investigation was conducted on a sample of 102 people, by using the Ego Structure Test described by G. Ammon (Ich-Struktur-Test nach Ammon (ISTA), 1997).
Results and discussion. This study showed that female patients with epilepsy had a more severity of destructive and deficient components of ego functions, such as aggression, fear, outer and inner ego demarcation, narcissism; sexual deficit as compared to normative data. The same was often noted at a statistically significant level in comparison with other study groups.
Conclusion. The impairment of all core functions in female patients with epilepsy leads to the impossible realization of mature sexuality.
The review presents an update on the electroencephalographic characteristics and neurophysiology of juvenile myoclonic epilepsy (JME) in Russia and foreign countries.
Materials and methods. The authors have performed a literary search for the full-text publications on JME electroencephalography and neurophysiology worldwide and in the Russian Federation, which are available in Russian and foreign databases.
Results and discussion. Analysis of the literature suggests that JME patients have some electroencephalographic pattern features that include the atypical morphology of spike-and-slow-wave complexes, as well as amplitude asymmetry, focal discharges, focal onset of paroxysms, focal paroxysmal shift, and generalized paroxysmal fast rhythm.
The analysis of the literature also indicates that primary care neurologists, clinical neurophysiologists, and epileptologists should be informed about the electroencephalographic characteristics of JME to timely diagnose the disease and to rule out the use of inadequate therapy.
Over the past decade, there has been a large amount of evidence indicating neuroendocrine, biochemical, and immune disorders in many acute and chronic central nervous system (CNS) diseases, including epilepsy, which made the authors consider the inflammatory theory of epileptogenesis. The chronic inflammatory process in epilepsy is believed to be facilitated by the activation of microglia and astrogliosis, which are accompanied by neuronal damage. The main postulate of this type of investigation is the assumption that the basis for CNS inflammation is blood-brain barrier (BBB) damage. Cytokines are presumed to play the greatest role in this process, mainly because they are natural pro- and anticonvulsants.
Patients and methods. Examinations were made in 160 patients with epilepsy (drug-resistant epilepsy (n = 80) and controlled epilepsy (n = 80)) and 30 apparently healthy donors. The blood and cerebrospinal fluid (CSF) levels of the cytokines interleukin (IL)-1β, IL-2, IL-6, IL-8, IL-10, tumor necrosis factor-α (TNF-α), IL-1 receptor antagonist (IL-1RA), soluble IL-2 receptor (sIL-2R), brain- derived neurotrophic factor (BDNF), S100b protein, С-reactive protein (CRP), and albumins were analyzed using a solid-phase enzyme-linked immunoabsorbent assay. Statistical analysis was performed using Student’s t-test and Mann-Whitney U-test. Differences at p <0.05 were regarded as statistically significant.
Results and discussion. The investigation showed that the patients with epilepsy had a substantially impaired plasma cytokine profile: higher levels of proinflammatory cytokines, such as Il-1β, IL-8, and TNF, and a lower concentration of IL-1 RA. The elevated CSF levels of the cytokines Il-1β and IL8 in patients with epilepsy suggest that BBB is impaired and a systemic inflammatory process exists while the absence of IL-1RA indicates that protective inflammation factors in blood and CSF are reduced.
Objective: to study and comparatively analyze the characteristics of social adaptation in reproductive-aged women with epilepsy and migraine in order to determine the social burden of the two most common neurological diseases.
Patients and methods. The present study is a continuation of a prospective observational uncontrolled study of the adverse effects of antiepileptic drugs on the reproductive health of epilepsy women, which has been conducted since 2015 according to Russian Foundation for Basic Research (RFBR) Grant No. 16-15-00281 and since 2018 according to RFBR Grant No. 18-013-00222. There are data on the comparative characteristics of social adaptation indicators in reproductive-aged women with epilepsy (n = 155) and migraine (n = 99).
Results and discussion. The reproductive-aged women with epilepsy were found to have a high educational level (only 7% had no secondary specialized or higher education). The unemployed were 30%; the disabled people were 23%. Migraine is more common in working women with a high educational level, has no disabling effect, but considerably reduces social activity and causes high unemployment rates. The severity of the main burden of neurological diseases is determined by medical and social indicators. Not only patients' health records, but also social adaptation, the indicators of which are criteria for treatment efficiency should be taken into consideration when evaluating the latter for epilepsy and
migraine.
The temporal lobe is the most epileptogenic region of the brain. 90% of patients with temporal ictal epileptomorphic EEG activity have a variable long history of seizures. Magnetic resonance spectroscopy (MRS) may be useful in identifying an epileptogenic focus in patients with epilepsy without apparent structural pathology at neuroimaging.
Objective: to systematize the results of early studies on this issue.
Materials and methods. An electronic search was carried out in two English-language (Medline, PubMed) and one Russian-language (eLIBRARY.RU) databases. The search queries found 18,019 citations, by which 12 full-text articles were selected.
Results and discussion. The main criteria for the diagnosis of temporal lobe epilepsy by MRS is to lower the level of N-acetylaspartate (NAA), the ratio of NAA to creatinine + choline (NAA/(Cr + Cho) in the brain region where there is neuronal death or damage, as well as a change in the level of myo-inositol, the elevated level of which indicates the presence of an epileptogenic focus, while the decreased one shows the spread of pathological activity to the adjacent tissues.
Conclusion. This review will contribute to a better diagnosis of temporal lobe epilepsy, as well as to the intravital noninvasive detection of metabolic changes in the brain long before the development of structural pathology.
CLINICAL OBSERVATONS
We have considered it appropriate to publish this case due to the rarity of progressive myoclonus epilepsy; diagnostic difficulties, particularly in the early stages of the disease (the female patient has been long followed up for diagnosed juvenile myoclonic epilepsy); the relative role of a genetic study because it has not brought results in this case, and, finally, a problem with therapy, and a significant contribution to the achievement of certain success of currently available antiepileptic drugs, levetiracetam in particular.
This paper describes a female patient aged 3 years 6 months with SYNGAP1-associated encephalopathy manifesting with symptomatic epilepsy, intellectual disability, and autism. There were difficulties in differential diagnosis, since in addition to SYNGAP1 mutation (c2214_2217deltgag), heterozygous BCKDHB gene mutation (chr6: 80910740G>a, rs3834233) and microduplication of a segment of chromosome 22 were found de novo. The features of the course and treatment of epilepsy in SYNGAP1 are discussed. A combination of valproic acid and oxcarbazepine was the most effective treatment for epilepsy.
Epileptic seizures require differential diagnosis with other paroxysmal conditions, including metabolic seizures. A variety of electrolyte changes can result in central nervous system dysfunction, including that as convulsive seizures. The paper describes electrolyte disorders leading to seizures, as well as their clinical features. It separately presents the syndromes accompanied by hypocalcemia, in which there may be convulsive paroxysms. The paper describes three clinical cases of hypocalcemic seizures. It gives recommendations for the diagnosis and management of patients with suspected metabolic seizures.
REVIEWS
A policy on generic substitutions, which is aimed at reducing the cost-effectiveness of pharmacotherapy, was proposed by the WHO at the end of the 20th century; however, but the debate about their economic benefits has continued until now. There have been the most active discussions of whether an epileptic patient may be switched from brand-name to generic antiepileptic drugs. The paper gives data obtained in Russian and foreign studies of the therapeutic efficacy and safety of anticonvulsant generics versus their brand- name drugs, as well as the impact of generic substitutions on the cost-effectiveness of antiepileptic therapy. Emphasis is placed on the importance of the quality of generic medicines, their dosage forms, and regulatory requirements for registration of generics. The problem of generic instability is under discussion.
The review is dedicated to the problems of current neurosurgical treatment for drug-resistant epilepsy in the adult population of Russia and foreign countries. The literature published in the period 2010–2017 was sought in Russian and foreign databases. This review included 58 only full-text publications. The search results have shown that despite advances in neurosurgery for drug-resistant epilepsy and the development of new surgical procedures, the problem of this disease has not yet been fully resolved today. This is evidenced by fairly high global prevalence rates in patients with postoperative epilepsy resistant to antiepileptic therapy. The literature analysis has revealed that the mean prevalence of postoperative epilepsy is 69%. This indicator may vary according to the type of an epileptogenic structural lesion and its location in the brain. However, despite the rapid development of epilepsy surgery, currently there is still a low surgical activity in the treatment of patients with drugresistant epilepsy. Of importance is also the presence of postoperative complications, including various infectious complications and neurological deficit. Taking into account the high rate of postoperative epilepsy, it is concluded that it is appropriate to develop postoperative rehabilitation methods for patients with drug-resistant epilepsy.
This literature review deals with knowledge and beliefs about epilepsy and with the attitude of patients, relatives, and society as a whole towards epilepsy. It discusses the stigma that is associated with the disease and has a strong impact on patients with epilepsy and their families. The problems of stigma or related concepts in different countries are analyzed.
ISSN 2310-1342 (Online)