Preview

Neurology, Neuropsychiatry, Psychosomatics

Advanced search
Vol 9, No 1S (2017): SPECIAL ISSUE: EPILEPSY
View or download the full issue PDF (Russian)
https://doi.org/10.14412/2074-2711-2017-1S

PHARMACOECONOMICS

4-10 228
Abstract
The paper deals with the problem of the interchangeability of brand-name and generic drugs. Touching upon official terminology and the normative documents that govern the registration of generics in Russia and foreign countries, the authors state that there is no concerted approach to estimating drug interchangeability, indicate that there are some disadvantages of using a method for proving the bioequivalence of the compared drugs as evidence for their therapeutic equivalence, and point out that Russia’s legal regulation of drug circulation lacks attention to the proper use of generics. The problem of interchangeability is particularly acute when prescribing narrow therapeutic range drugs, including anticonvulsant drugs. The results of the investigations discussed in the article demonstrate the need for a very cautious approach to using generic drugs in the therapy of epilepsy due to the fact that the disease may worsen. The authors come to the conclusion that treatment with less expensive generic drugs is far from always more economical. The change from a brand-name for a generic drug should be carefully approached, basing on the data of properly designed and conducted studies of therapeutic equivalence.

ORIGINAL INVESTIGATIONS

11-20 330
Abstract

Objective: to analyze the efficacy and tolerability of sustained-release sodium valproate (SV) in adult patients with focal or generalized epilepsy in real clinical practice in three regions (Krasnoyarsk, Moscow, and Samara) of the Russian Federation.

Patients and methods. The investigation enrolled adult patients with focal (n=63) or generalized (n=31) epilepsy who had received a stable dose of the drug alone (n=64 (68%)) or in combination with one of the antiepileptic drugs (AEDs): levetiracetam, lamotrigine, topiramate, or perampanel (n=30 (31.9%)) for at least one year. According to the brand name of drugs, their use frequency was as follows: Depakine® Chrono (61.7%), Convulex® (16%), Depakine® Chronosphere (9.6%), Valparine® XP (8.5%), and Encorate® Chrono (4.3%).

Results. For a period of over one year, most patients with focal epilepsy (FE) (49.2%) and idiopathic generalized epilepsy (IGE) (67.7%) achieved a remission of seizures when they used moderate (1000 mg) and low (<1000 mg) daily doses of SV. Among the PE and IGE patients taking Depakine Chronosphere, the remission rate was highest, amounting to 100 and 75%, respectively. The efficacy of SV in both FE and IGE decreased in the following order: Depakine Chrono, Convulex, and Valparine XP. Clinical remission was achieved in none of the patients taking Encorate Chrono.

The most common unwanted side reactions (USRs) were weight gain, menstrual disorders, tremor, and hair loss; however, their total frequency (16%) proved to be substantially lower than previously considered. The side effects were observed in one-half of the patients receiving a daily SV dose of 1000 mg and more, USRs were noted during combination therapy with SV medications and topiramate (n=5) or lamotrigine (n=2). USRs were frequently observed in the heterozygous carriers of the single nucleotide polymorphisms (SNPs) CYP2C9*3 (27.3%) versus those who had the common (wild-type) allele variant CYP2C9*1, but USRs were recorded mainly in the heterozygous carriers of CYP2C9*3 and CYP2C9*2 who received low daily doses of SV.

The frequency of the CYP2C9 gene among SNPs proved to be highest: CYP2C9*1/*1 in 68 (72.3%) patients, CYP2C9*2 in 14 (14.9%), and CYP2C9*3 in 11 (11.7%). The compound heterozygous CYP2C9*2/*3 genotype was recorded in one (1.06%) case.

The inadequate effect of AEDs requires therapeutic drug monitoring (TDM); and to rule out USRs calls for pharmacogenetic studies before or at the early stages of titration of SV, by determining its starting dosage, titration rate, and therapeutic dose. TDM and a pharmacogenetics study allow optimization of the personalized choice of AEDs. 

21-25 14710
Abstract

The use of antiepileptic drugs (AEDs) during pregnancy is associated with an increased risk of congenital malformations (CMF). Information on the teratogenicity of AEDs is contradictory. The potential negative effects of new-generation AEDs are less well known. Many physicians and patients face difficulties in establishing a balance between the risk of seizures during pregnancy and that of teratogenicity in the use of AEDs. In most foreign countries, there are national and international pregnancy and epilepsy registries that make possible to centralize and systematize information on the safety of AEDs and to also give a true picture of the state of the problem.

The Russian pregnancy and epilepsy register (RPER) has been launched since 2017. RPER is a Russian national prospective and retrospective observational study, without interfering with the antiepileptic therapy prescribed by an attending physician to childbearing-aged patients living in the subjects of the Russian Federation. RPER is an independent research initiative and is implemented by neurologists and psychiatrists who provide assistance to women with epilepsy. The main goal of the RPER is to compare the risk of serious CMFs following the maternal intake of various AEDs and their combinations in different regions of the Russian Federation and to develop strategies for preventing CMFs. 

26-31 230
Abstract

The article presents information on the definition of juvenile myoclonic epilepsy (JME) and current epidemiological data concerning its prevalence in Russia and foreign countries.

Objective: to study the available publications on the epidemiological monitoring of JME worldwide and in the Russian Federation.

Material and methods. Available full-text publications were sought in Russian and foreign databases.

Results. It has been found that to date, there are no clear reliable data on the prevalence and incidence of JME and there is also evidence to believe that the real incidence of the disease is significantly higher due to the fact that JME is hypodiagnosed. This suggests that epidemiological studies should be conducted in the regions according to the common criteria, by establishing a register of patients with epilepsy.

Conclusion. Analysis of the literature suggests that there is a need for the epidemiological monitoring of JME in order to elaborate personalized approaches to prediction, prevention, diagnosis, treatment, and follow-up of this group of patients, especially those with a family history. 

32-38 144
Abstract

Objective: to study the characteristics of manifestations of hormonal abnormalities in women with juvenile myoclonic epilepsy (JME) and to comparatively analyze identified syndromes.

Patients and methods. Hormonal disorders were analyzed in 48 reproductive-aged women with JME, who had received antiepileptic drug (AED) mono- and bitherapy during one or more years.

Results. 66.7% of the patients were found to have ovarian hormonal dysfunction manifesting itself as the development of polycystic ovary syndrome, hypogonadism, isolated hyperandrogenism, and hypoprogesteronemia. Clinically detected syndromes frequently appeared as menstrual irregularity in 29% of the patients. Comparative analysis of hormone-dependent syndromes showed that there were no differences in the clinical features of JME, but the earliest age at onset in isolated hyperandrogenism, and no patients with menstrual irregularity in the presence of isolated hypoprogesteronemia. The use of different AEDs had no impact on the incidence of hormonal abnormalities, which requires further investigation and its inclusion of a greater number of patients receiving various AEDs. 

39-47 186
Abstract

Objective: to reveal the prevalence of cognitive impairment and emotional disorders (anxiety and depression) in patients with juvenile myoclonic epilepsy (JME) and to evaluate the role of a hormonal background, taken antiepileptic drugs (AEDs), and the course of the disease in the genesis of found abnormalities.

Patients and methods. The prevalence of cognitive impairment and emotional-affective disorders was analyzed in 48 female patients with JME.

Results and discussion. Decreased cognitive functions according to the Montreal Cognitive Assessment were detected in 12 (40%) patients. The greatest difficulties were faced by the patients when they carried out the tasks used to examine memory and abstract thinking. The level of anxiety and depression was assessed using the Hospital Anxiety and Depression Scale (HADS) and the Beck Depression Inventory (BDI). The HADS showed the subclinical manifestations of depression in 10 (33.3%) patients and their obvious ones in 4 (13.4%). The subclinical manifestations of depression, assessed by HADS scores, were detected in 4 (13.3%) patients; its obvious manifestations were absent. BDI scores indicated that there were minimal, mild, moderate, and severe manifestations in 6 (20%), 3 (10%), 2 (6.7%), and 1 patients, respectively. Cognitive functions and the level of anxiety and depression did not depend on the patients’ age at disease onset and at the time of investigation, disease duration, menstrual cycle regularity, therapy regimen, and hormonal status. However, all the patients tended to have lower estradiol and higher progesterone and testosterone levels as cognitive and emotional disorders increased. Myoclonic seizures in conjunction with generalized tonic-clonic seizures significantly more frequently led to cognitive and emotional-affective disorders. Cognitive and emotional disorders occurred in patients without remission and depended on the nature of seizures. The absence of differences between the groups of patients treated with various antiepileptic drugs (AEDs) is due to the fact that most patients received valproates (n = 19) or monotherapy (n = 26), and the number of patients taking other AEDs proved to be incomparably small. 

48-53 141
Abstract

Objective: to analyze our clinical experience with perampanel (PER), by evaluating the efficacy, tolerability, and individual choice priorities.

Patients and methods. The investigation enrolled 28 patients with drug-resistant focal epilepsy; the patients' mean age was 38.3±10.7 years. The proportion of men was 46.4%; the disease duration was 8 to 33 years (mean 20.2 years). Antiepileptic drugs (AEDs) were changed 7–10 times in 66% of the patients and 5–6 times in 23%. The efficacy and tolerability of AEDs and the electroclinical features of epilepsy were compared in two groups: responders and non-responders.

Results and discussion. The responder and non-responder groups had a substantial preponderance of patients with frontal lobe epilepsy and diffuse epileptiform electroencephalographic (EEG) patterns (80%:46% and 80%:38%, respectively; p = 0.0001), but those with temporal lobe epilepsy and isolated regional EEG patterns were 2–3 times fewer (20%: 53.8% and 20%:61.5%; p = 0.0001). Only one of 10 combinations of carbamazepine (CBM) and PER was successful. Aggression, fear, and psychosis, which occurred in 5 (17.8%) patients taking PER 2–6 mg/day, were the most common adverse reactions associated with its discontinuation. PER is an effective agent to overcome of drug resistance in epilepsy. The benefit of the drug is that it may be used in undifferentiated antiepileptic therapy regimens. When predicting the effects of PER, preliminary switch from CBZ to oxcarbazepine or eslicarbazepine is reasonable. 

54-57 185
Abstract

Objective: to investigate the level of intellectual development in children born to mothers with epilepsy.

Patients and methods. The Wechsler test was used to examine 30 epileptic mother–child pairs (a study group) and 10 healthy mother–child ones (a control group). The children’s mean age was 8 years 9 months in the study group and 7 years 8 months in the control group.

Results. In the children from the study group, the general, verbal and non-verbal intelligence quotient (IQ) scores were 126.6, 112.3, and 136.2, respectively. There were no statistically significant differences in IQ scores between the two groups of children. The comparison of the IQ scores in children who did not take antiepileptic drugs and those who received valproic acid and carbamazepine showed no statistical differences. The IQ was comparable or higher in the children than that in their mothers with epilepsy.

Conclusion. The IQ scores in the children born to epileptic mothers are moderate and higher and do not differ from those in the children born to healthy mothers. 

58-63 166
Abstract

The complex characterization of patients with epilepsy involves a description of their psychological sphere, quality of life, and a response to ongoing anticonvulsant therapy.

Objective: to study the heterogeneity of a group of patients with epilepsy in terms of the indicators of emotional and cognitive disorders, social adaptation, and a response to ongoing anticonvulsant therapy in order to identify criteria for rating these spheres.

Patients and methods. 110 patients with epilepsy were examined. The levels of anxiety and depression, cognitive functions, and quality of life were assessed using the SF-36 and QOLIE-31 questionnaires, as well as the number of seizures and that of taken anticonvulsants were estimated. Multivariate statistical methods were used to divide the patients into subgroups.

Results. Based on the examined characteristics, the investigators identified patient subgroups differing in the level of anxiety and depression, the characteristics of cognitive functions, quality of life, and a response to ongoing therapy with anticonvulsants, established a relationship between these characteristics and the form of epilepsy, and proposed criteria for rating these disorders. The heterogeneity of a group of patients with epilepsy was established using the examined characteristics; the higher level of cognitive impairment, the low efficiency of anticonvulsant therapy and the level of social adaptation were described in patients with symptomatic epilepsy. 

CLINICAL OBSERVATIONS

64-68 233
Abstract
The article presents a case of childhood absence epilepsy concurrent with mysophobia, panic attacks, and the development of alternative psychosis in an accentuated girl with drug-induced remission of absence seizures and EEG changes.
69-73 164
Abstract
Generalized convulsive status epilepticus (GCSE) is the most dangerous type of status epilepticus. The paper describes a clinical case of a 33-year-old female patient admitted to an intensive care unit for diagnosed ischemic stroke in the posterior cerebral artery bed and GCSE. EEG showed diffuse discharges of epileptiform activity against a flattened background (an EEG correlate of the terminal phase of status epilepticus). Intensive treatment was performed; the outcome of the disease was fatal. The article discusses the possible causes of status epilepticus and its treatment policy in the patient.
74-77 163
Abstract
The paper describes a 6-year-old female patient with epilepsy caused by mutations in the SCN2A and PCDH19 genes, which clinically appears as epileptic seizures, drug-resistant epilepsy, secondary microcephaly, mental retardation, and autism. It reviews the literature regarding both mutations. World literature lacks publications on a combination of two SCN2A and PCDH19 mutations in one female patient with epileptic encephalopathies.

REVIEWS

78-83 215
Abstract
The paper gives an update on the impact of stigmatization on the quality of life and daily activity of patients with epilepsy. The cognitive beliefs of society and patients, which are associated with the etiology and course of the disease, are considered. Cultural and gender differences in the perception of epilepsy are pointed out.
84-88 189
Abstract
The article considers the arguments that can provide a rationale for treatment policy in patients with epilepsy after failure of monotherapy with a first antiepileptic drug (AED). When choosing alternative monotherapy or early polytherapy with AEDs, one should consider a diversity of criteria: the mechanism of action, pharmacokinetic and pharmacodynamic properties, efficacy, and safety profile of AEDs, disease features, individual patient characteristics, and social factors. The choice of the right AED treatment policy in the early stages of the disease is important for patients because the inadequate control of seizures can result in irreversible psychosocial consequences and reduce the chance to eliminate future disabling seizures.
89-96 222
Abstract
The risks associated with in utero antiepileptic drug (AED) exposure are of great importance for both epileptic women and their offspring. This review considers the basic mechanisms of valproate-induced teratogenesis. It discusses the mechanisms of fetal valproic acid accumulation, oxidative stress, folate antagonism, and histone deacetylase inhibition. Analysis of the literature has shown a large number of studies that prove and disprove different mechanisms of valproate-induced teratogenesis. Histone deacetylase inhibition and oxidative stress have the most pronounced teratogenic effect; moreover, both mechanisms are particularly important in the first trimester of pregnancy when DNA dysregulation has the greatest impact on organogenesis. All the described mechanisms (and possibly many others) along with individual genetic characteristics, environmental factors, and lifestyle, each of which has not been defined, may lead to an increased risk for the teratogenic effects of valproic acid.
97-100 224
Abstract
The paper considers the classification of epilepsy and epileptic syndromes. It discusses the place of cryptogenic (probably symptomatic) epilepsy among the epileptic syndromes, the current approach to defining cryptogenic epilepsy, and the features of the latter in adults.


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2074-2711 (Print)
ISSN 2310-1342 (Online)