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The epidemiology of epilepsy in the Russian Federation
Epilepsy Research (2010) 92, 209—218
journal homepage: www.elsevier.com/locate/epilepsyres
The epidemiology of epilepsy in the Russian Federation Alla Guekht a,∗, W. Allen Hauser b, Larissa Milchakova a, Yury Churillin a, Alexander Shpak c, Eugene Gusev a a
Department of Neurology and Neurosurgery, Russian State Medical University, Leninsky Prospect 8, block 8, Moscow, 119049, Russia b Departments of Neurology, Epidemiology and Sergievsky Center, Columbia University, 630 W 168th Street, New York, NY 10032, USA c The S.Fyodorov Eye Microsurgery Complex — Federal State Institution, Beskudnikovsky bulv, 59A, Moscow, 127486, Russia Received 2 December 2009; received in revised form 18 September 2010; accepted 26 September 2010 Available online 28 October 2010
KEYWORDS Prevalence; Epilepsy; Seizure; Russian Federation; Etiology
Summary This study is the first analysis of the epidemiology of epilepsy in the Russian Federation (RF), in the English medical literature. The RF is geographically the largest territory in the world with a population of 142 million. The study evaluated prevalence of epilepsy in older teenagers and adults in 14 regions of the RF with total population of 517,624 persons (about 0.34% of all the population of the RF). Study sites were located in both European (Western population) and Siberian (Eastern population) regions of Russia. We identified 1753 patients with established epilepsy (1033 men, 720 women) from available medical information sources. Epilepsy cases were evaluated by study neurologists or epileptologists; all the patients underwent EEG, one third — neuroimaging. The age adjusted prevalence of epilepsy, standardized to the European Standard Million was 3.40 (95%CI: 3.26—3.55) per 1000. Prevalence was higher among men—–4.50 (95%CI: 4.25—4.76) than among women—–2.52 (95%CI: 2.35—2.69) (p < 0.0001). Prevalence in the Eastern population was significantly higher than in the Western population. The highest prevalence was found in the age group 50—59 years. Localization-related (focal) epilepsies/epilepsy syndromes were diagnosed in the majority (81.6%). In about one-third of those with localization-related epilepsies etiology remained undetermined. Head injury was the main identified cause of epilepsy, followed by cerebrovascular disorders. Conclusion: The prevalence of epilepsy in the population ≥14 y.o. in Russia is consistent with results of the studies in adults in other European countries, although at lower end of the range. Age and gender trends are similar. © 2010 Elsevier B.V. All rights reserved.
∗
Corresponding author. Tel.: +7 495 236 96 58; fax: +7 495 236 91 11. E-mail addresses: [email protected], [email protected] (A. Guekht), [email protected] (W.A. Hauser), a [email protected] (A. Shpak). 0920-1211/$ — see front matter © 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.eplepsyres.2010.09.011
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Introduction Epilepsy is a common neurological disorder and is associated with substantial burden on physical and mental health. Epilepsy interferes with social functioning by limiting employment, educational opportunities, and interpersonal relationships and can increase the risk for death. Populationbased epidemiological studies on epilepsy are available mainly from the West European, Baltic and Western Mediterranean countries. (Hauser et al., 1993; Olafsson et al., 1996; Olafsson and Hauser, 1999; Jacoby et al., 2005). According to a recently published systematic review (Forsgren et al., 2005), the prevalence of active epilepsy in these studies of all ages varied from 3.3 to 7.8 per 1000 inhabitants. Studies limited to adults with active epilepsy have been reported from three countries in northern Europe—–Finland (Keranen et al., 1989), Sweden (Forsgren, 1992) and Estonia (Oun et al., 2003). Prevalence of active epilepsy ranged from 5.3 to 6.3 per 1000 inhabitants. No studies were identified from large areas of Europe, especially from the Eastern Europe. The general profile of epilepsy in Russia was, until recently, mostly unknown. The results of several epidemiological studies (Borinevich and Averbakh, 1967; Morozov and Kerimov, 1988; Belov and Kazakovtsev, 1991) were published only in Russian, reflected the situation in the USSR several decades ago. Further, each study covered only a single region of the country. The present paper presents the results of a series of studies in different regions of Russia, each performed with the same protocol. These local studies investigated the prevalence of epilepsy, clinical profiles, seizure types, clinical syndromes, etiology, seizure frequency, therapy, educational level and social status of the adolescent and adult (14 years and older) patients with active epilepsy. According to the Guidelines for epidemiologic studies on epilepsy by the Commission on Epidemiology and Prognosis of the International League Against Epilepsy (ILAE), active case of epilepsy was defined as a person who has had two or more seizures, at least one of them in the previous 5 years, regardless of any antiepileptic drug (AED) treatment.
Methods Study population Areas, where the study has been performed, were located in European (Western population) and Siberian (Eastern population) regions of the Russian Federation (RF). These regions have differences in demography, economics and culture. In both the Western and the Eastern regions the prevalence was determined in the different types of communities: big cities, towns, and rural areas. The Western population studied included Moscow city, Moscow suburbs, Yaroslavl and Ekaterinburg. The Eastern population included Irkutsk city, Bratsk and Republic of Burjatia. In each area one or several study regions were selected with a population representative for the given area, both regarding the sample size and the social/ethnic structure.
A. Guekht et al. Sample size was calculated using a formula n = (t2 pq)/d2 where n is the minimum sample size, t is the score on a gaussian distribution correspondent with a certain confidence level (we used t = 3.3), p is the presumed prevalence of the disease (0.005), q = 1 − p, and d is the desired level of precision (we accepted d = 0.001). Accordingly, the sample size for Russia should be not less than 54,200 (3.32 × 0.005 × 0.995/0.0012 ). Bearing in mind the huge territory of the country and variety of economic, cultural, ethnic particularities, sample size was calculated separately for the regions: Moscow city, Moscow region, Yaroslavl, Ekaterinburg, Irkutsk city, Bratsk and Republic of Burjatia, that gives the total minimal sample size of 350,000 inhabitants. The actual population for this study was 517,624. Attempts were made to collect the information about all the patients with epilepsy in the selected areas. Letters from health authorities in each of the areas were obtained with the agreement to provide all the necessary information to the study team, including access to multiple data sources including medical records from hospitals, outpatient departments and emergency care units. Screening of medical records in the outpatient departments was especially useful, as medical information was stored there for the substantial part of the population. To update the information about patients with established epilepsy, patient’s visits to one of the members of the study group were scheduled or, in if not possible, telephone interviews were conducted. Patients were classified as having epilepsy based upon clinical evaluation and EEG findings. Study neurologists reviewed the medical history of all patients with previously established active epilepsy. If there were doubts regarding the accuracy of the diagnosis, new visits were scheduled with clinical and EEG examination. For each patient, a questionnaire was completed, including demographic data, possible etiologic factors, clinical pattern of epilepsy, results of neurological examination, of EEG, and other investigations, therapy. According to the Guidelines for epidemiologic studies on epilepsy (1993), epilepsy was defined as the condition characterized by recurrent (two or more) epileptic seizures, unprovoked by any immediate identified cause. Multiple seizures occurring in a 24-h period were considered a single event. All patients with epilepsy had clinical evaluation and EEG. CT or MRI investigations were performed in about one-third of patients. Information was obtained about educational level and social status. Newly identified patients were followed up for 1 year at by one of the members of the study group. A prevalent case of active epilepsy was defined as a person with epilepsy who has had at least one seizure in the previous 5 years, regardless of antiepileptic drug treatment. All cases were classified according to the ILAE Classification of epileptic seizures (1981), and the Classification of epilepsies and epileptic syndromes (1989). Etiology was considered as presumed in our study and was determined on the basis on history, clinical data and available routine neuroimaging studies. The limitation of this study was that, because of economic reasons, more appro-
The epidemiology of epilepsy in the Russian Federation Table 1
Men Women All
211
Standardized prevalence rate of epilepsy (Russian Federation, Western and Eastern populations), per 1000. Russian Federation
Western population
Eastern population
Prevalence
95% CI
Prevalence
95% CI
Prevalence
95% CI
4.50 2.52 3.40
4.25—4.76 2.35—2.69 3.26—3.55
3.91 1.94 2.82
3.58—4.26 1.75—2.16 2.64—3.01
5.27 3.21 4.12
4.87—5.70 2.93—3.51 3.88—4.36
priate neuroimaging studies, metabolic screenings, and genetic analysis were not available. We categorized people by etiology based upon the Guidelines for epidemiologic studies on epilepsy (1993). Cases were classified as remote symptomatic unprovoked seizures if conditions resulting in a static encephalopathy were identified. This included individuals with epilepsy subsequent to brain insult, such as CNS infection, brain trauma, cerebrovascular disease, pre- and perinatal disorders. The following etiological characteristics were applied: head injury, cerebrovascular disease, CNS infection, pre- and perinatal disorders. People were classified as having a progressive symptomatic epilepsy when unprovoked seizures were considered related to neurodegenerative diseases, such as Alzheimer disease.
Data analysis Data from regional studies (population, age and gender distribution, identified cases of epilepsy, prevalence values, age of onset, seizure types, syndromes and epilepsy, seizure frequency, etiology, AED treatment, educational level and social status) were summarized. Age standardized (direct standardization with European Standard Million standard population (Surveillance Epidemiology and End Results (SEER) of the National Cancer Institute) prevalence of the active epilepsy with its’ 95% confidence intervals for total population, and age and gender specific prevalence were calculated (Fay and Feuer, 1997; Krieger et al., 2004). Ageadjusted prevalence was also calculated independently for the Western and the Eastern populations and the regions included. The mean and 95% confidence interval for continuous variables were calculated, as were proportions for categorical variables. Continuous variables were compared with the use of the Students’ t-test. Two proportions were compared with Z-test or with the ϕ-Fisher transformation √ (ϕ = 2 arcsin p) with Yeats’ corrections (Sergienko and Bondareva, 2001) and Students’ t-test. For homogeneity test of categorical variable distributions Chi-square test was used.
Results The study population comprised 14 regions with a total population 517,624 (about 0.34% of all the population of the RF). One thousand seven hundred and fifty three patients age 14 and over with established epilepsy were identified (1033 men, 720 women). Seven hundred and sixty five patients with epilepsy (461 men, 304 women) were identified in the Western areas, 988 patients (572 men, 416 women) in the
p-Value Western vs Eastern
<0.0001 <0.0001 <0.0001
Eastern regions. The mean age of patients was 38.27 (95%CI: 37.27—39.15) y.o. There were no significant differences of the mean age between men (38.12 -95%CI: 36.9—39.34) and women (38.43 -95%CI: 37.17—39.69) (p = 0.73).
Prevalence of epilepsy The age adjusted prevalence for epilepsy (in the population 14 y.o and older) in the Russian Federation, with standardization to the European Standard Million was 3.40 (95%CI: 3.26—3.55) per 1000 and was higher among men—– 4.50 (95%CI: 4.25—4.76) than among women—–2.52 (95%CI: 2.35—2.69) (p < 0.0001). Prevalence in the Eastern population was significantly higher than in the Western population, gender-specific prevalence was higher in the Eastern population compared to the Western population (p < 0.001) (Table 1). The prevalence for men was higher than for women. (p < 0.001). The highest prevalence was found for the age group 50—59 years (Fig. 1A—C). The prevalence difference between Western and Eastern populations was significant for the age-related prevalence profile for all patients (2 = 146.6; df = 6; p < 0.0001), men (2 = 50.3; df = 6; p < 0.0001) and women (2 = 112.9; df = 6; p < 0.0001). Age specific prevalence was significantly higher in the Eastern population when compared with the west for several age strata: for men in the age groups 30—39 y.o. (p < 0.0001), 40—49 y.o. (p = 0.0011), and 50—59 y.o. (p = 0.023): for women in age groups 14—29 y.o (p = 0.0036), 30—39 y.o. (p = 0.025), 40—49 y.o. and 50—59 y.o. (p < 0.0001), and 60—69 y.o. (p = 0.033).
Types of epilepsies/epilepsy syndromes and seizure Localization-related (focal) epilepsies/epilepsy syndromes were diagnosed in the majority of prevalence cases (1430 out of 1753, 81.6%) while generalized epilepsy syndromes—–accounted for 18.4%. The proportion of prevalence cases with localization-related epilepsies and epilepsy syndromes was significantly lower in the Eastern population (79.4%) than in the Western population (84.3%) (p = 0.0086) (Table 2). The great majority of patients in both populations had partial seizures (simple, complex, or partial with secondarily generalization). More detailed breakdown of seizure types is presented in Table 3. The difference in overall proportion of seizure types between the Western and the Eastern populations was significant (2 = 20.5; df = 7; p = 0.0053). Still, there were no
212
A. Guekht et al.
Figure 2 Frequency of seizures in the Russian Federation (RF), Western and Eastern populations. Differences between the Eastern and the Western populations are significant, p < 0.001.
seizure-free for >1 year (Fig. 2). There were significant differences in the proportion of seizure-free patients in the Eastern (4.8%) and the Western (14.0%) populations (p < 0.001). Accordingly, the proportion of patients with 12 and more seizure per year in the Eastern population was significantly higher (p < 0.001).
Etiology of epilepsy Epilepsy in patients with generalized epilepsy syndromes was unknown in the vast majority of cases and would have been considered idiopathic in the 1989 syndrome classification scheme. Special attention was paid to the analysis of possible etiological factors in patients with localization-related epilepsies. In the study population (age ≥ 14 y.o.) etiology of epilepsy was undetermined in about one-third: 37.2% of the Eastern population, 29.8% of the Western population, p = 0.003) (Fig. 3).
Figure 1 Age and gender-specific prevalence rate of epilepsy for the (A) Russian Federation, (B) Western population and (C) Eastern population. Data are expressed as prevalence rate and CI 95%.
differences in pairwise comparison of all types of seizure (p > 0.08) with the exception of tonic seizure (p = 0.039).
Seizure frequency Patients in both populations had rather frequent seizures. About half (48.1%) of patients had 12 seizures and more per year, 43.1%—–from 1 to 12 seizures per year, 8.8% were
Figure 3 Etiology of epilepsy in patients with localizationrelated epilepsies and epilepsy syndromes. Data are expressed as proportion rate and CI 95%. There are significant differences in the rates of the patients with unknown etiology (p = 0.003), cerebrovascular diseases (p = 0.0045) and neurodegenerative disorders (p = 0.0035) between the Eastern and the Western populations, as well as for the etiological factors profiles (p < 0.001) for the Western and the Eastern populations.
The epidemiology of epilepsy in the Russian Federation
213
Table 2 Localization-related and generalized epilepsies and epilepsy syndromes in the Russian Federation, Western and Eastern populations age 14 and over.
Russian Federation Western population Eastern population
Localization-related epilepsy syndromes
Generalized epilepsy syndromes
N
%
N
%
81.6 84.3 79.4
323 120 203
18.4 15.7 20.6
1,430 645 785
1753 765 988
The most frequently prescribed drugs were carbamazepine, phenobarbital and valproic acid. For patients on monotherapy, carbamazepine was prescribed in 36.7% of cases: phenobarbital, 28.5%; valproic acid, 26.2%; phenytoin, 2%, topiramate, 3.6%; lamotrigine, 2.0%, and other AEDs < 1%. For prevalence cases on polytherapy, carbamazepine was used in 89.1%, phenobarbital in 71.3%, and valproic acid in 42.6%. Less than 5% of prevalence cases were treated with newer AEDs. New AEDs were prescribed mostly in big cities, and phenobarbital was prescribed predominantly in rural areas, especially in the Eastern regions.
Traumatic brain injury was the main identified cause of epilepsy (27.7% of cases). The proportion of prevalence cases attributable to brain injury was similar in the Eastern (28.4%) and the Western (26.8%) populations (p = 0.501). Cerebrovascular disease was identified as the etiology of epilepsy in 12.3% prevalence cases with localization-related epilepsies (15.0% in the Western population, 10.1% in the Eastern population, p = 0.0045). Neurodegenerative disease accounted for 1.61% of prevalence cases in the total population (2.6% in the Western population, 0.8% in the Eastern population, p = 0.0035). Other etiological factors including pre/perinatal disorders (12.0%), CNS infection (7.8%), tumors (4.8%) did not show significant differences in overall proportions when the Eastern and Western populations were compared. Still, there were significant differences in the etiology factors profiles for the Western and the Eastern populations (2 = 62; df = 7; p < 0.001).
Educational level The educational level of prevalence cases (PWE) was lower than that of the general Russian Federation, with a higher proportion with minimal education and a lower-proportion with university/college education (Table 4) (2 = 14.9; df = 3; p = 0.002) (All-Russian Population Census, 2002). There were also differences in the educational level of prevalence cases in the Western population when compared to the Eastern population. The proportion with only primary education or less was similar in both populations, but the proportion of PWE with university/college education was higher in the Western compared to the Eastern population (p < 0.0001), and, accordingly, the proportion of patients, which graduated from the secondary school—–lower in the Western vs the Eastern population (p < 0.0001).
Treatment The majority of prevalence cases were taking medications: 44.1% were taking one AED, 38.7% received two or more AEDs, but 17.2% of prevalence cases were untreated. There was a small, but significant difference in proportion of patients, receiving monotherapy (40.9% versus 46.8%) in the Western vs the Eastern populations (p = 0.041). There were no differences between Eastern and Western populations in the proportion untreated or the proportion on polytherapy.
Table 3
Total
Distribution of prevalence cases age 14 and over by predominant seizure types.
Seizure type
RF
Western population
Eastern population
%
N
%
N
%
323 44 16 96 19 148
18.4 2.5 0.9 5.5 1.1 8.4
120 18 6 35 4 57
15.7 2.4 0.8 4.6 0.5 7.4
203 26 10 61 15 91
20.6 2.7 1.0 6.2 1.5 9.2
1430 67 132 1231
81.6 3.8 7.6 70.2
645 36 64 545
84.3 4.7 8.4 71.2
785 31 68 686
79.4 3.1 6.9 69.4
N Generalized onset seizures Myoclonic Atonic Absence Tonic Tonic—clonic Partial seizures Partial simple Partial complex Partial (simple and/ or complex) evolving to generalized
214 Table 4
A. Guekht et al. Educational level among prevalence cases with epilepsy age 14 and over. Total RF (population)
No (minimal) education 1.0% Primary school 7.8% Secondary school 71.9% Higher education 19.3%
Total RF (PWE)
p-Value (population vs PWE)
Western population (PWE)
Eastern population (PWE)
p-Value (Western vs Eastern)
1.7% 6.1% 75.6% 16.6%
0.041 0.036 0.008 0.025
2.1% 6.7% 67.5% 23.7%
1.5% 5.8% 80.3% 12.4%
0.520 0.560 <0.0001 <0.0001
Social status There was a high proportion of disabled people (57.1%) among PWE compared to the general population (8.4%) (p < 0.0001) (Fig. 4). Only 20.9% of PWE were working and 8.7% were unemployed compared to 51.4% and 3.9% respectively in the general population (p < 0.0001). There was no difference of proportion of students (7.2%) among PWE compared to general population (7.9%) (p = 0.27) (AllRussian Population Census, 2002; Healthcare in the Russian Federation, 2005; Federal State Statistics Service of the RF). The occupational profile was more favorable in the Western population: the proportion of PWE employed or studying was significantly higher (p < 0.001) and the proportion of disabled was significantly lower (p < 0.001) in the Western areas compared to the Eastern (Table 5).
Discussion This study is the first description in the English medical literature of the epidemiology of epilepsy in the Russian Federation. Design of the study was determined by the huge territory of the country and variety of economic, cultural, ethnic, geographical differences, which made it necessary to collect data from many different areas in the country. All the efforts were made to select the study population representative of the general population of people with epilepsy in the Russian Federation. The actual sample size of this study was 517,624 (about 0.34% of all the population of the
Figure 4 Occupational profile of PWE and general population in the Russian Federation.
RF); areas in the Western and Eastern part of the country were included. The age adjusted prevalence rate for epilepsy for older adolescents and adults in the Russian Federation, with standardization to the European Standard Million was 3.40 (95%CI: 3.26—3.55) per 1000 and was higher among men than women. Overall, in North America and in Europe, active age adjusted epilepsy prevalence ranges between 5 and 10 per 1000 (Banerjee et al., 2009). The prevalence of active epilepsy in Europe for all ages varied from 3.3 to 7.8 per 1000 inhabitants in different studies (Forsgren et al., 2005). Gallitto et al. (2005) reported even lower prevalence rate— –3.01 per 1000. Overall, the prevalence of epilepsy in the population ≥14 y.o. in Russia is consistent with results of the studies in adults in other European countries, although at lower end of the range. We suppose, that some patients with epilepsy might have been missed because of misdiagnosis or not coming under medical observation; lower prevalence might also reflect certain degree of stigma and, consequently, concealment. Still, our data on epilepsy prevalence are significantly higher compared to the official data of the Ministry of Health (1.7 per 1000), which are based mostly on data from patient visits to different medical institutions. Geographically Russia is located in both Europe and Asia, that is why we compared prevalence rates in the areas in both parts of the country. Prevalence in the Eastern population (4.1 per 1000) was significantly higher than in the Western population (2.8). Prevalence of epilepsy in Asia was recently reviewed by Mac et al. (2007): it varied among countries from 1.5 to 14.0 per 1000, with the median rate estimated at 6 per 1000. Still, the comparison with other Asian countries is rather difficult, because of the different climates (Asian Russia—–Siberia, is well-known for its severe climate with cold winters), and ethnicity of population (mostly Caucasians in Siberia, with Yacuts and Buriats in some areas). The highest prevalence in our study was found in the age group 50—59 years. Though many European studies report the highest prevalence rates in the elderly (Olafsson and Hauser, 1999; Luengo et al., 2001; Rocca et al., 2001), many others (Granieri et al., 1983; Joensen, 1986; Keranen et al., 1989; Oun et al., 2003) demonstrated lower prevalence in the elderly vs adults. Median prevalence was 5.4/1000 in the age groups 20—59 y.o vs 4.7/1000 in the age group 60+ in the European review (Forsgren et al., 2005). It was hypothesized by those author that identification of cases amongst the elderly was less complete as for other age groups and that most studies underestimated prevalence rates for the elderly. This may also be the case for our study.
The epidemiology of epilepsy in the Russian Federation Table 5
215
Social status of people with epilepsy.
Workers Office-workers Students Unemployed Pensioners Disabled
Total RF
Western
Eastern
p-Value (Western vs Eastern)
11.5% 9.4% 7.2% 8.7% 6.1% 57.1%
17.6% 14.1% 8.8% 7.6% 12.5% 39.4%
8.4% 7.0% 6.4% 9.2% 2.8% 66.2%
<0.0001 <0.0001 0.092 0.293 <0.0001 <0.0001
In accordance with the majority of other studies, we found higher prevalence for men compared to women (Sillanpaa, 1973; Granieri et al., 1983; Maremmani et al., 1991; Giuliani et al., 1992; Endziniene et al., 1997; Beilmann et al., 1999; Olafsson and Hauser, 1999; Waaler et al., 2000). In our study, localization-related (focal) epilepsies/epilepsy syndromes were diagnosed in the majority of patients (81.6%) while generalized epilepsy syndromes—–in 18.4%. As summarized by Forsgren et al. (2005), there were 55—83% cases with partial seizures or localization-related epilepsies in studies in adults and the elderly in Europe (Keranen et al., 1989; Forsgren, 1992; de la Court et al., 1996; Oun et al., 2003). Prevalence cases in our study, had rather frequent seizures—–48.1% patients had 12 seizures and more per year. Indeed, high proportion of patients with frequent seizures and the predominance of patients with secondarily generalized seizures might suggest an underascertainment of cases with rare partial seizures. As epilepsy in patients with generalized epilepsy syndromes was unknown and would have been considered idiopathic using older classifications. Special attention was paid to the analysis of possible etiological factors in patients with localization-related epilepsies. The proportion of localization-related or focal prevalence cases with unknown etiology of epilepsy was 33.9%; head injury was the main identified cause of epilepsy (27.7% of cases), followed by cerebrovascular diseases (12.3%), pre/perinatal disorders (12.0%) and CNS infection (7.8%). It is important to mention, that the study included only persons over 14 y.o and this may have influenced this distribution. The etiological profile of epilepsy was similar to other studies, with the substantial proportion of cases with unknown etiology. Compared to other European studies, there was higher proportion of patients with epilepsy after brain injury, though similar proportions were reported by Oun et al. (2003) in Estonia. High prevalence of post-traumatic epilepsy (20% of all the symptomatic epilepsies) has been observed in China by Li et al. (2004). Still, direct comparison was not possible, as data on the proportions of presumed causes of epilepsy were mostly collected in the in population-based incidence studies (Olafsson et al., 1996; Forsgren et al., 1996; Sander et al., 1990; Oun et al., 2003). Also, proportion of patients with epilepsy after brain injury could be associated with high incidence and severity of brain trauma in Russia. A systematic review of brain injury epidemiology in Europe (Tagliaferri et al., 2006) presents incidence rate of the traumatic brain injury about 235 per 100,000 with the average mortality rate of about 15 per 100,000 and severity ratio of hospitalized patients was about
22:1.5:1 for mild vs. moderate vs. severe cases, respectively. In Russia the incidence of head trauma is reported as 457 per 100,000 with mortality rate of about 20% and up to 50% of moderate and severe cases (Federal State Statistics Service of the Russian Federation, 2003—2008). The correlation between the incidence of epilepsy after brain trauma and its severity has been established in many studies (Angeleri et al., 1999; Annegers et al., 1998; Englander et al., 2003; Ferguson et al., 2010). The relative role of pre/perinatal disorders (12.0%) and CNS infection (7.8%) was greater in the current study when compared to other prevalence studies (Hauser et al., 1996). The proportion of patients with epilepsy, presumably caused by cerebrovascular diseases and neurodegenerative diseases was significantly higher in the Western compared to the Eastern population, that could be explained by greater proportion of prevalence cases over 50 y.o. in the Western population. The study demonstrated that there is a necessity to improve the system of epilepsy care in the country. The great majority of patients were on AED treatment, with almost equal proportion on monotherapy and polytherapy; however, 17.2% of patients with active epilepsy were untreated. The most frequently prescribed drugs were carbamazepine and phenobarbital, followed by valproic acid (twice less frequently prescribed). Interestingly, the rather similar treatment pattern was described by Gallitto et al. (2005) at Aeolian Islands. In the UK study phenytoin and carbamazepine were also the most commonly preferred first line drugs followed by valproate, and carbamazepine was the most frequently prescribed for patients with partial seizures (Lhatoo et al., 2001). In spite of treatment of more than 80% of prevalence cases, the proportion seizure-free was extremely low—–8.8%, and even lower in the Eastern part of the country, perhaps because of inadequate treatment regimens, and poor compliance. In the Soviet Union (until 1990 Russia was one of the Soviet republics) educational system, the majority of people graduated from the secondary school, so the educational levels were good in both in the general population and the prevalence cases (more than 70% had secondary education). Still, there were significant differences in the whole pattern (or profile) of the educational status between the general population and epilepsy prevalence cases. The educational level of patients was lower in comparison with the overall population of the Russian Federation, with higher proportion with minimal education and a lower-proportion with university/college education among the epilepsy prevalence cases. The proportion of persons with higher education was substantially lower in the Eastern vs Western regions.
216 The employment status of prevalence cases of epilepsy was dramatically different from that of the general populations, with the majority of prevalence cases being on disability. There are several explanations for this finding. High level of disability is related to the relatively frequent seizures in many patients; still, there is a substantial impact of the particularities of the healthcare system. The disability status is attractive for the patient as it facilitates the access to free medications and some other social benefits. This status is especially important for patients in the Eastern regions, with really limited possibilities to find appropriate work (that is why the proportion of employed patients is twice lower in that area). Compared to data from the Western Europe, the employment status was more significantly affected (Shackleton, 2003). There were obvious differences in the educational level and social status in PWE in comparison to the general population. Our data showed that the educational level and the social status of PWE was better in the Western Eastern regions of Russia than in the Eastern. It might too some extent reflect the differences in social, economical as well as geographic conditions between the Western and the Eastern parts of the Russian Federation. (In general, Western areas are more developed economically and have better organized social infrastructure; however, straightforward comparison is not possible. For instance, the proportion of students and number of universities are higher in the Western areas, but there is a substantial number of students from Eastern areas in these universities.) There are more possibilities for employment for PWE in the Western part, with many closely situated cities and towns with lots of positions in different offices and smallscale enterprises, relatively mild climate, better developed system of healthcare, compared to the Eastern areas, were cities and towns are at the distance of hundreds kilometers between them, with predominance of big industrial plants and factories, with stern climate with very cold winters; in that areas the status of a disabled person becomes sometimes the only source of financial and social benefits. The educational and social status of epilepsy patients is widely discussed in the literature, with the special attention to the negative effect on the social identity of people with the disorder, related to stigma. Reduction of stigma associated with epilepsy worldwide is a major focus of the current WHO/ILAE/IBE Global Campaign (Scott et al., 2001; Reynolds, 2002; Beghi et al., 2002; Jacoby et al., 2004, 2005; Dua et al., 2006). Frequent underachievements in patients with epilepsy were demonstrated in many studies. (Verity and Ross, 1985; Britten et al., 1986; Sturniolo and Galletti, 1994). A significantly higher unemployment rate was found in PWE than among age- and gender-matched controls (Elwes et al., 1991). The higher unemployment, underemployment, or unskilled work rate, demonstrated amongst PWE by the RESt-1 Group, was in stark contrast with their better education (The RESt-1 Group, 2000). Unemployment and underemployment in people with epilepsy are related to a variety of factors, including associated neurological and neuropsychological problems (Rodin et al., 1972; Sillanpaa, 1994; Batzel et al., 1980). On the other hand, low socioeconomic status, as indexed by low education or lack of home ownership, was a risk factor for epilepsy in adults (Hesdorffer et al., 2005).
A. Guekht et al. As mentioned above, our study has certain limitations. Because of the huge territories involved and differences in geographic, ethnic, cultural practices of the study areas, some people with epilepsy, especially milder cases and elderly patients, may have been missed. Huge size and population of the country with 83 administrative territories and the impressive difference between them in many aspects, including substantial variations of population density between and within these territories, caused another limitation. As described in Section ‘‘Study population’’, we also had to take into consideration different types of communities, ethnic and other peculiarities, so the study was performed in 14 regions located in 6 administrative territories. We understand that our estimations of the prevalence of the epilepsy to the RF were rather rough. However, it was the first study that allowed to estimate the range of prevalence values in the RF and evaluate the difference between the Western and Eastern areas of the country. Further studies on epidemiology of epilepsy in specific regions in Russia will provide more detailed information
Conclusion The present study was the first to address prevalence and other basic epidemiologic data regarding epilepsy in the Russian Federation. The present investigation shows that the prevalence of epilepsy in the population ≥ 14 y.o. in Russia is consistent with results of the studies in adults in other European countries, although at lower end of the range. Age and gender trends are similar. The great majority of patients were on AED treatment, with almost equal proportion on monotherapy and polytherapy. Still, about one out of five patients with active epilepsy were not taking any AED. Special attention to improvement on epilepsy care, especially in the Eastern regions of the country, is required.
Acknowledgment We are grateful to our colleagues from the study regions of the Russian Federation: Balkhanova R.N., Boiko A.N., Golovanova I.V., Kabakov R.M., Kotov A.S., Kotov S.V., Pisova N.V., Perunova N.N., Shprach V.V., Spirin N.N., and Volkova L.I. for their invaluable collaboration.
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journal homepage: www.elsevier.com/locate/epilepsyres
The epidemiology of epilepsy in the Russian Federation Alla Guekht a,∗, W. Allen Hauser b, Larissa Milchakova a, Yury Churillin a, Alexander Shpak c, Eugene Gusev a a
Department of Neurology and Neurosurgery, Russian State Medical University, Leninsky Prospect 8, block 8, Moscow, 119049, Russia b Departments of Neurology, Epidemiology and Sergievsky Center, Columbia University, 630 W 168th Street, New York, NY 10032, USA c The S.Fyodorov Eye Microsurgery Complex — Federal State Institution, Beskudnikovsky bulv, 59A, Moscow, 127486, Russia Received 2 December 2009; received in revised form 18 September 2010; accepted 26 September 2010 Available online 28 October 2010
KEYWORDS Prevalence; Epilepsy; Seizure; Russian Federation; Etiology
Summary This study is the first analysis of the epidemiology of epilepsy in the Russian Federation (RF), in the English medical literature. The RF is geographically the largest territory in the world with a population of 142 million. The study evaluated prevalence of epilepsy in older teenagers and adults in 14 regions of the RF with total population of 517,624 persons (about 0.34% of all the population of the RF). Study sites were located in both European (Western population) and Siberian (Eastern population) regions of Russia. We identified 1753 patients with established epilepsy (1033 men, 720 women) from available medical information sources. Epilepsy cases were evaluated by study neurologists or epileptologists; all the patients underwent EEG, one third — neuroimaging. The age adjusted prevalence of epilepsy, standardized to the European Standard Million was 3.40 (95%CI: 3.26—3.55) per 1000. Prevalence was higher among men—–4.50 (95%CI: 4.25—4.76) than among women—–2.52 (95%CI: 2.35—2.69) (p < 0.0001). Prevalence in the Eastern population was significantly higher than in the Western population. The highest prevalence was found in the age group 50—59 years. Localization-related (focal) epilepsies/epilepsy syndromes were diagnosed in the majority (81.6%). In about one-third of those with localization-related epilepsies etiology remained undetermined. Head injury was the main identified cause of epilepsy, followed by cerebrovascular disorders. Conclusion: The prevalence of epilepsy in the population ≥14 y.o. in Russia is consistent with results of the studies in adults in other European countries, although at lower end of the range. Age and gender trends are similar. © 2010 Elsevier B.V. All rights reserved.
∗
Corresponding author. Tel.: +7 495 236 96 58; fax: +7 495 236 91 11. E-mail addresses: [email protected], [email protected] (A. Guekht), [email protected] (W.A. Hauser), a [email protected] (A. Shpak). 0920-1211/$ — see front matter © 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.eplepsyres.2010.09.011
210
Introduction Epilepsy is a common neurological disorder and is associated with substantial burden on physical and mental health. Epilepsy interferes with social functioning by limiting employment, educational opportunities, and interpersonal relationships and can increase the risk for death. Populationbased epidemiological studies on epilepsy are available mainly from the West European, Baltic and Western Mediterranean countries. (Hauser et al., 1993; Olafsson et al., 1996; Olafsson and Hauser, 1999; Jacoby et al., 2005). According to a recently published systematic review (Forsgren et al., 2005), the prevalence of active epilepsy in these studies of all ages varied from 3.3 to 7.8 per 1000 inhabitants. Studies limited to adults with active epilepsy have been reported from three countries in northern Europe—–Finland (Keranen et al., 1989), Sweden (Forsgren, 1992) and Estonia (Oun et al., 2003). Prevalence of active epilepsy ranged from 5.3 to 6.3 per 1000 inhabitants. No studies were identified from large areas of Europe, especially from the Eastern Europe. The general profile of epilepsy in Russia was, until recently, mostly unknown. The results of several epidemiological studies (Borinevich and Averbakh, 1967; Morozov and Kerimov, 1988; Belov and Kazakovtsev, 1991) were published only in Russian, reflected the situation in the USSR several decades ago. Further, each study covered only a single region of the country. The present paper presents the results of a series of studies in different regions of Russia, each performed with the same protocol. These local studies investigated the prevalence of epilepsy, clinical profiles, seizure types, clinical syndromes, etiology, seizure frequency, therapy, educational level and social status of the adolescent and adult (14 years and older) patients with active epilepsy. According to the Guidelines for epidemiologic studies on epilepsy by the Commission on Epidemiology and Prognosis of the International League Against Epilepsy (ILAE), active case of epilepsy was defined as a person who has had two or more seizures, at least one of them in the previous 5 years, regardless of any antiepileptic drug (AED) treatment.
Methods Study population Areas, where the study has been performed, were located in European (Western population) and Siberian (Eastern population) regions of the Russian Federation (RF). These regions have differences in demography, economics and culture. In both the Western and the Eastern regions the prevalence was determined in the different types of communities: big cities, towns, and rural areas. The Western population studied included Moscow city, Moscow suburbs, Yaroslavl and Ekaterinburg. The Eastern population included Irkutsk city, Bratsk and Republic of Burjatia. In each area one or several study regions were selected with a population representative for the given area, both regarding the sample size and the social/ethnic structure.
A. Guekht et al. Sample size was calculated using a formula n = (t2 pq)/d2 where n is the minimum sample size, t is the score on a gaussian distribution correspondent with a certain confidence level (we used t = 3.3), p is the presumed prevalence of the disease (0.005), q = 1 − p, and d is the desired level of precision (we accepted d = 0.001). Accordingly, the sample size for Russia should be not less than 54,200 (3.32 × 0.005 × 0.995/0.0012 ). Bearing in mind the huge territory of the country and variety of economic, cultural, ethnic particularities, sample size was calculated separately for the regions: Moscow city, Moscow region, Yaroslavl, Ekaterinburg, Irkutsk city, Bratsk and Republic of Burjatia, that gives the total minimal sample size of 350,000 inhabitants. The actual population for this study was 517,624. Attempts were made to collect the information about all the patients with epilepsy in the selected areas. Letters from health authorities in each of the areas were obtained with the agreement to provide all the necessary information to the study team, including access to multiple data sources including medical records from hospitals, outpatient departments and emergency care units. Screening of medical records in the outpatient departments was especially useful, as medical information was stored there for the substantial part of the population. To update the information about patients with established epilepsy, patient’s visits to one of the members of the study group were scheduled or, in if not possible, telephone interviews were conducted. Patients were classified as having epilepsy based upon clinical evaluation and EEG findings. Study neurologists reviewed the medical history of all patients with previously established active epilepsy. If there were doubts regarding the accuracy of the diagnosis, new visits were scheduled with clinical and EEG examination. For each patient, a questionnaire was completed, including demographic data, possible etiologic factors, clinical pattern of epilepsy, results of neurological examination, of EEG, and other investigations, therapy. According to the Guidelines for epidemiologic studies on epilepsy (1993), epilepsy was defined as the condition characterized by recurrent (two or more) epileptic seizures, unprovoked by any immediate identified cause. Multiple seizures occurring in a 24-h period were considered a single event. All patients with epilepsy had clinical evaluation and EEG. CT or MRI investigations were performed in about one-third of patients. Information was obtained about educational level and social status. Newly identified patients were followed up for 1 year at by one of the members of the study group. A prevalent case of active epilepsy was defined as a person with epilepsy who has had at least one seizure in the previous 5 years, regardless of antiepileptic drug treatment. All cases were classified according to the ILAE Classification of epileptic seizures (1981), and the Classification of epilepsies and epileptic syndromes (1989). Etiology was considered as presumed in our study and was determined on the basis on history, clinical data and available routine neuroimaging studies. The limitation of this study was that, because of economic reasons, more appro-
The epidemiology of epilepsy in the Russian Federation Table 1
Men Women All
211
Standardized prevalence rate of epilepsy (Russian Federation, Western and Eastern populations), per 1000. Russian Federation
Western population
Eastern population
Prevalence
95% CI
Prevalence
95% CI
Prevalence
95% CI
4.50 2.52 3.40
4.25—4.76 2.35—2.69 3.26—3.55
3.91 1.94 2.82
3.58—4.26 1.75—2.16 2.64—3.01
5.27 3.21 4.12
4.87—5.70 2.93—3.51 3.88—4.36
priate neuroimaging studies, metabolic screenings, and genetic analysis were not available. We categorized people by etiology based upon the Guidelines for epidemiologic studies on epilepsy (1993). Cases were classified as remote symptomatic unprovoked seizures if conditions resulting in a static encephalopathy were identified. This included individuals with epilepsy subsequent to brain insult, such as CNS infection, brain trauma, cerebrovascular disease, pre- and perinatal disorders. The following etiological characteristics were applied: head injury, cerebrovascular disease, CNS infection, pre- and perinatal disorders. People were classified as having a progressive symptomatic epilepsy when unprovoked seizures were considered related to neurodegenerative diseases, such as Alzheimer disease.
Data analysis Data from regional studies (population, age and gender distribution, identified cases of epilepsy, prevalence values, age of onset, seizure types, syndromes and epilepsy, seizure frequency, etiology, AED treatment, educational level and social status) were summarized. Age standardized (direct standardization with European Standard Million standard population (Surveillance Epidemiology and End Results (SEER) of the National Cancer Institute) prevalence of the active epilepsy with its’ 95% confidence intervals for total population, and age and gender specific prevalence were calculated (Fay and Feuer, 1997; Krieger et al., 2004). Ageadjusted prevalence was also calculated independently for the Western and the Eastern populations and the regions included. The mean and 95% confidence interval for continuous variables were calculated, as were proportions for categorical variables. Continuous variables were compared with the use of the Students’ t-test. Two proportions were compared with Z-test or with the ϕ-Fisher transformation √ (ϕ = 2 arcsin p) with Yeats’ corrections (Sergienko and Bondareva, 2001) and Students’ t-test. For homogeneity test of categorical variable distributions Chi-square test was used.
Results The study population comprised 14 regions with a total population 517,624 (about 0.34% of all the population of the RF). One thousand seven hundred and fifty three patients age 14 and over with established epilepsy were identified (1033 men, 720 women). Seven hundred and sixty five patients with epilepsy (461 men, 304 women) were identified in the Western areas, 988 patients (572 men, 416 women) in the
p-Value Western vs Eastern
<0.0001 <0.0001 <0.0001
Eastern regions. The mean age of patients was 38.27 (95%CI: 37.27—39.15) y.o. There were no significant differences of the mean age between men (38.12 -95%CI: 36.9—39.34) and women (38.43 -95%CI: 37.17—39.69) (p = 0.73).
Prevalence of epilepsy The age adjusted prevalence for epilepsy (in the population 14 y.o and older) in the Russian Federation, with standardization to the European Standard Million was 3.40 (95%CI: 3.26—3.55) per 1000 and was higher among men—– 4.50 (95%CI: 4.25—4.76) than among women—–2.52 (95%CI: 2.35—2.69) (p < 0.0001). Prevalence in the Eastern population was significantly higher than in the Western population, gender-specific prevalence was higher in the Eastern population compared to the Western population (p < 0.001) (Table 1). The prevalence for men was higher than for women. (p < 0.001). The highest prevalence was found for the age group 50—59 years (Fig. 1A—C). The prevalence difference between Western and Eastern populations was significant for the age-related prevalence profile for all patients (2 = 146.6; df = 6; p < 0.0001), men (2 = 50.3; df = 6; p < 0.0001) and women (2 = 112.9; df = 6; p < 0.0001). Age specific prevalence was significantly higher in the Eastern population when compared with the west for several age strata: for men in the age groups 30—39 y.o. (p < 0.0001), 40—49 y.o. (p = 0.0011), and 50—59 y.o. (p = 0.023): for women in age groups 14—29 y.o (p = 0.0036), 30—39 y.o. (p = 0.025), 40—49 y.o. and 50—59 y.o. (p < 0.0001), and 60—69 y.o. (p = 0.033).
Types of epilepsies/epilepsy syndromes and seizure Localization-related (focal) epilepsies/epilepsy syndromes were diagnosed in the majority of prevalence cases (1430 out of 1753, 81.6%) while generalized epilepsy syndromes—–accounted for 18.4%. The proportion of prevalence cases with localization-related epilepsies and epilepsy syndromes was significantly lower in the Eastern population (79.4%) than in the Western population (84.3%) (p = 0.0086) (Table 2). The great majority of patients in both populations had partial seizures (simple, complex, or partial with secondarily generalization). More detailed breakdown of seizure types is presented in Table 3. The difference in overall proportion of seizure types between the Western and the Eastern populations was significant (2 = 20.5; df = 7; p = 0.0053). Still, there were no
212
A. Guekht et al.
Figure 2 Frequency of seizures in the Russian Federation (RF), Western and Eastern populations. Differences between the Eastern and the Western populations are significant, p < 0.001.
seizure-free for >1 year (Fig. 2). There were significant differences in the proportion of seizure-free patients in the Eastern (4.8%) and the Western (14.0%) populations (p < 0.001). Accordingly, the proportion of patients with 12 and more seizure per year in the Eastern population was significantly higher (p < 0.001).
Etiology of epilepsy Epilepsy in patients with generalized epilepsy syndromes was unknown in the vast majority of cases and would have been considered idiopathic in the 1989 syndrome classification scheme. Special attention was paid to the analysis of possible etiological factors in patients with localization-related epilepsies. In the study population (age ≥ 14 y.o.) etiology of epilepsy was undetermined in about one-third: 37.2% of the Eastern population, 29.8% of the Western population, p = 0.003) (Fig. 3).
Figure 1 Age and gender-specific prevalence rate of epilepsy for the (A) Russian Federation, (B) Western population and (C) Eastern population. Data are expressed as prevalence rate and CI 95%.
differences in pairwise comparison of all types of seizure (p > 0.08) with the exception of tonic seizure (p = 0.039).
Seizure frequency Patients in both populations had rather frequent seizures. About half (48.1%) of patients had 12 seizures and more per year, 43.1%—–from 1 to 12 seizures per year, 8.8% were
Figure 3 Etiology of epilepsy in patients with localizationrelated epilepsies and epilepsy syndromes. Data are expressed as proportion rate and CI 95%. There are significant differences in the rates of the patients with unknown etiology (p = 0.003), cerebrovascular diseases (p = 0.0045) and neurodegenerative disorders (p = 0.0035) between the Eastern and the Western populations, as well as for the etiological factors profiles (p < 0.001) for the Western and the Eastern populations.
The epidemiology of epilepsy in the Russian Federation
213
Table 2 Localization-related and generalized epilepsies and epilepsy syndromes in the Russian Federation, Western and Eastern populations age 14 and over.
Russian Federation Western population Eastern population
Localization-related epilepsy syndromes
Generalized epilepsy syndromes
N
%
N
%
81.6 84.3 79.4
323 120 203
18.4 15.7 20.6
1,430 645 785
1753 765 988
The most frequently prescribed drugs were carbamazepine, phenobarbital and valproic acid. For patients on monotherapy, carbamazepine was prescribed in 36.7% of cases: phenobarbital, 28.5%; valproic acid, 26.2%; phenytoin, 2%, topiramate, 3.6%; lamotrigine, 2.0%, and other AEDs < 1%. For prevalence cases on polytherapy, carbamazepine was used in 89.1%, phenobarbital in 71.3%, and valproic acid in 42.6%. Less than 5% of prevalence cases were treated with newer AEDs. New AEDs were prescribed mostly in big cities, and phenobarbital was prescribed predominantly in rural areas, especially in the Eastern regions.
Traumatic brain injury was the main identified cause of epilepsy (27.7% of cases). The proportion of prevalence cases attributable to brain injury was similar in the Eastern (28.4%) and the Western (26.8%) populations (p = 0.501). Cerebrovascular disease was identified as the etiology of epilepsy in 12.3% prevalence cases with localization-related epilepsies (15.0% in the Western population, 10.1% in the Eastern population, p = 0.0045). Neurodegenerative disease accounted for 1.61% of prevalence cases in the total population (2.6% in the Western population, 0.8% in the Eastern population, p = 0.0035). Other etiological factors including pre/perinatal disorders (12.0%), CNS infection (7.8%), tumors (4.8%) did not show significant differences in overall proportions when the Eastern and Western populations were compared. Still, there were significant differences in the etiology factors profiles for the Western and the Eastern populations (2 = 62; df = 7; p < 0.001).
Educational level The educational level of prevalence cases (PWE) was lower than that of the general Russian Federation, with a higher proportion with minimal education and a lower-proportion with university/college education (Table 4) (2 = 14.9; df = 3; p = 0.002) (All-Russian Population Census, 2002). There were also differences in the educational level of prevalence cases in the Western population when compared to the Eastern population. The proportion with only primary education or less was similar in both populations, but the proportion of PWE with university/college education was higher in the Western compared to the Eastern population (p < 0.0001), and, accordingly, the proportion of patients, which graduated from the secondary school—–lower in the Western vs the Eastern population (p < 0.0001).
Treatment The majority of prevalence cases were taking medications: 44.1% were taking one AED, 38.7% received two or more AEDs, but 17.2% of prevalence cases were untreated. There was a small, but significant difference in proportion of patients, receiving monotherapy (40.9% versus 46.8%) in the Western vs the Eastern populations (p = 0.041). There were no differences between Eastern and Western populations in the proportion untreated or the proportion on polytherapy.
Table 3
Total
Distribution of prevalence cases age 14 and over by predominant seizure types.
Seizure type
RF
Western population
Eastern population
%
N
%
N
%
323 44 16 96 19 148
18.4 2.5 0.9 5.5 1.1 8.4
120 18 6 35 4 57
15.7 2.4 0.8 4.6 0.5 7.4
203 26 10 61 15 91
20.6 2.7 1.0 6.2 1.5 9.2
1430 67 132 1231
81.6 3.8 7.6 70.2
645 36 64 545
84.3 4.7 8.4 71.2
785 31 68 686
79.4 3.1 6.9 69.4
N Generalized onset seizures Myoclonic Atonic Absence Tonic Tonic—clonic Partial seizures Partial simple Partial complex Partial (simple and/ or complex) evolving to generalized
214 Table 4
A. Guekht et al. Educational level among prevalence cases with epilepsy age 14 and over. Total RF (population)
No (minimal) education 1.0% Primary school 7.8% Secondary school 71.9% Higher education 19.3%
Total RF (PWE)
p-Value (population vs PWE)
Western population (PWE)
Eastern population (PWE)
p-Value (Western vs Eastern)
1.7% 6.1% 75.6% 16.6%
0.041 0.036 0.008 0.025
2.1% 6.7% 67.5% 23.7%
1.5% 5.8% 80.3% 12.4%
0.520 0.560 <0.0001 <0.0001
Social status There was a high proportion of disabled people (57.1%) among PWE compared to the general population (8.4%) (p < 0.0001) (Fig. 4). Only 20.9% of PWE were working and 8.7% were unemployed compared to 51.4% and 3.9% respectively in the general population (p < 0.0001). There was no difference of proportion of students (7.2%) among PWE compared to general population (7.9%) (p = 0.27) (AllRussian Population Census, 2002; Healthcare in the Russian Federation, 2005; Federal State Statistics Service of the RF). The occupational profile was more favorable in the Western population: the proportion of PWE employed or studying was significantly higher (p < 0.001) and the proportion of disabled was significantly lower (p < 0.001) in the Western areas compared to the Eastern (Table 5).
Discussion This study is the first description in the English medical literature of the epidemiology of epilepsy in the Russian Federation. Design of the study was determined by the huge territory of the country and variety of economic, cultural, ethnic, geographical differences, which made it necessary to collect data from many different areas in the country. All the efforts were made to select the study population representative of the general population of people with epilepsy in the Russian Federation. The actual sample size of this study was 517,624 (about 0.34% of all the population of the
Figure 4 Occupational profile of PWE and general population in the Russian Federation.
RF); areas in the Western and Eastern part of the country were included. The age adjusted prevalence rate for epilepsy for older adolescents and adults in the Russian Federation, with standardization to the European Standard Million was 3.40 (95%CI: 3.26—3.55) per 1000 and was higher among men than women. Overall, in North America and in Europe, active age adjusted epilepsy prevalence ranges between 5 and 10 per 1000 (Banerjee et al., 2009). The prevalence of active epilepsy in Europe for all ages varied from 3.3 to 7.8 per 1000 inhabitants in different studies (Forsgren et al., 2005). Gallitto et al. (2005) reported even lower prevalence rate— –3.01 per 1000. Overall, the prevalence of epilepsy in the population ≥14 y.o. in Russia is consistent with results of the studies in adults in other European countries, although at lower end of the range. We suppose, that some patients with epilepsy might have been missed because of misdiagnosis or not coming under medical observation; lower prevalence might also reflect certain degree of stigma and, consequently, concealment. Still, our data on epilepsy prevalence are significantly higher compared to the official data of the Ministry of Health (1.7 per 1000), which are based mostly on data from patient visits to different medical institutions. Geographically Russia is located in both Europe and Asia, that is why we compared prevalence rates in the areas in both parts of the country. Prevalence in the Eastern population (4.1 per 1000) was significantly higher than in the Western population (2.8). Prevalence of epilepsy in Asia was recently reviewed by Mac et al. (2007): it varied among countries from 1.5 to 14.0 per 1000, with the median rate estimated at 6 per 1000. Still, the comparison with other Asian countries is rather difficult, because of the different climates (Asian Russia—–Siberia, is well-known for its severe climate with cold winters), and ethnicity of population (mostly Caucasians in Siberia, with Yacuts and Buriats in some areas). The highest prevalence in our study was found in the age group 50—59 years. Though many European studies report the highest prevalence rates in the elderly (Olafsson and Hauser, 1999; Luengo et al., 2001; Rocca et al., 2001), many others (Granieri et al., 1983; Joensen, 1986; Keranen et al., 1989; Oun et al., 2003) demonstrated lower prevalence in the elderly vs adults. Median prevalence was 5.4/1000 in the age groups 20—59 y.o vs 4.7/1000 in the age group 60+ in the European review (Forsgren et al., 2005). It was hypothesized by those author that identification of cases amongst the elderly was less complete as for other age groups and that most studies underestimated prevalence rates for the elderly. This may also be the case for our study.
The epidemiology of epilepsy in the Russian Federation Table 5
215
Social status of people with epilepsy.
Workers Office-workers Students Unemployed Pensioners Disabled
Total RF
Western
Eastern
p-Value (Western vs Eastern)
11.5% 9.4% 7.2% 8.7% 6.1% 57.1%
17.6% 14.1% 8.8% 7.6% 12.5% 39.4%
8.4% 7.0% 6.4% 9.2% 2.8% 66.2%
<0.0001 <0.0001 0.092 0.293 <0.0001 <0.0001
In accordance with the majority of other studies, we found higher prevalence for men compared to women (Sillanpaa, 1973; Granieri et al., 1983; Maremmani et al., 1991; Giuliani et al., 1992; Endziniene et al., 1997; Beilmann et al., 1999; Olafsson and Hauser, 1999; Waaler et al., 2000). In our study, localization-related (focal) epilepsies/epilepsy syndromes were diagnosed in the majority of patients (81.6%) while generalized epilepsy syndromes—–in 18.4%. As summarized by Forsgren et al. (2005), there were 55—83% cases with partial seizures or localization-related epilepsies in studies in adults and the elderly in Europe (Keranen et al., 1989; Forsgren, 1992; de la Court et al., 1996; Oun et al., 2003). Prevalence cases in our study, had rather frequent seizures—–48.1% patients had 12 seizures and more per year. Indeed, high proportion of patients with frequent seizures and the predominance of patients with secondarily generalized seizures might suggest an underascertainment of cases with rare partial seizures. As epilepsy in patients with generalized epilepsy syndromes was unknown and would have been considered idiopathic using older classifications. Special attention was paid to the analysis of possible etiological factors in patients with localization-related epilepsies. The proportion of localization-related or focal prevalence cases with unknown etiology of epilepsy was 33.9%; head injury was the main identified cause of epilepsy (27.7% of cases), followed by cerebrovascular diseases (12.3%), pre/perinatal disorders (12.0%) and CNS infection (7.8%). It is important to mention, that the study included only persons over 14 y.o and this may have influenced this distribution. The etiological profile of epilepsy was similar to other studies, with the substantial proportion of cases with unknown etiology. Compared to other European studies, there was higher proportion of patients with epilepsy after brain injury, though similar proportions were reported by Oun et al. (2003) in Estonia. High prevalence of post-traumatic epilepsy (20% of all the symptomatic epilepsies) has been observed in China by Li et al. (2004). Still, direct comparison was not possible, as data on the proportions of presumed causes of epilepsy were mostly collected in the in population-based incidence studies (Olafsson et al., 1996; Forsgren et al., 1996; Sander et al., 1990; Oun et al., 2003). Also, proportion of patients with epilepsy after brain injury could be associated with high incidence and severity of brain trauma in Russia. A systematic review of brain injury epidemiology in Europe (Tagliaferri et al., 2006) presents incidence rate of the traumatic brain injury about 235 per 100,000 with the average mortality rate of about 15 per 100,000 and severity ratio of hospitalized patients was about
22:1.5:1 for mild vs. moderate vs. severe cases, respectively. In Russia the incidence of head trauma is reported as 457 per 100,000 with mortality rate of about 20% and up to 50% of moderate and severe cases (Federal State Statistics Service of the Russian Federation, 2003—2008). The correlation between the incidence of epilepsy after brain trauma and its severity has been established in many studies (Angeleri et al., 1999; Annegers et al., 1998; Englander et al., 2003; Ferguson et al., 2010). The relative role of pre/perinatal disorders (12.0%) and CNS infection (7.8%) was greater in the current study when compared to other prevalence studies (Hauser et al., 1996). The proportion of patients with epilepsy, presumably caused by cerebrovascular diseases and neurodegenerative diseases was significantly higher in the Western compared to the Eastern population, that could be explained by greater proportion of prevalence cases over 50 y.o. in the Western population. The study demonstrated that there is a necessity to improve the system of epilepsy care in the country. The great majority of patients were on AED treatment, with almost equal proportion on monotherapy and polytherapy; however, 17.2% of patients with active epilepsy were untreated. The most frequently prescribed drugs were carbamazepine and phenobarbital, followed by valproic acid (twice less frequently prescribed). Interestingly, the rather similar treatment pattern was described by Gallitto et al. (2005) at Aeolian Islands. In the UK study phenytoin and carbamazepine were also the most commonly preferred first line drugs followed by valproate, and carbamazepine was the most frequently prescribed for patients with partial seizures (Lhatoo et al., 2001). In spite of treatment of more than 80% of prevalence cases, the proportion seizure-free was extremely low—–8.8%, and even lower in the Eastern part of the country, perhaps because of inadequate treatment regimens, and poor compliance. In the Soviet Union (until 1990 Russia was one of the Soviet republics) educational system, the majority of people graduated from the secondary school, so the educational levels were good in both in the general population and the prevalence cases (more than 70% had secondary education). Still, there were significant differences in the whole pattern (or profile) of the educational status between the general population and epilepsy prevalence cases. The educational level of patients was lower in comparison with the overall population of the Russian Federation, with higher proportion with minimal education and a lower-proportion with university/college education among the epilepsy prevalence cases. The proportion of persons with higher education was substantially lower in the Eastern vs Western regions.
216 The employment status of prevalence cases of epilepsy was dramatically different from that of the general populations, with the majority of prevalence cases being on disability. There are several explanations for this finding. High level of disability is related to the relatively frequent seizures in many patients; still, there is a substantial impact of the particularities of the healthcare system. The disability status is attractive for the patient as it facilitates the access to free medications and some other social benefits. This status is especially important for patients in the Eastern regions, with really limited possibilities to find appropriate work (that is why the proportion of employed patients is twice lower in that area). Compared to data from the Western Europe, the employment status was more significantly affected (Shackleton, 2003). There were obvious differences in the educational level and social status in PWE in comparison to the general population. Our data showed that the educational level and the social status of PWE was better in the Western Eastern regions of Russia than in the Eastern. It might too some extent reflect the differences in social, economical as well as geographic conditions between the Western and the Eastern parts of the Russian Federation. (In general, Western areas are more developed economically and have better organized social infrastructure; however, straightforward comparison is not possible. For instance, the proportion of students and number of universities are higher in the Western areas, but there is a substantial number of students from Eastern areas in these universities.) There are more possibilities for employment for PWE in the Western part, with many closely situated cities and towns with lots of positions in different offices and smallscale enterprises, relatively mild climate, better developed system of healthcare, compared to the Eastern areas, were cities and towns are at the distance of hundreds kilometers between them, with predominance of big industrial plants and factories, with stern climate with very cold winters; in that areas the status of a disabled person becomes sometimes the only source of financial and social benefits. The educational and social status of epilepsy patients is widely discussed in the literature, with the special attention to the negative effect on the social identity of people with the disorder, related to stigma. Reduction of stigma associated with epilepsy worldwide is a major focus of the current WHO/ILAE/IBE Global Campaign (Scott et al., 2001; Reynolds, 2002; Beghi et al., 2002; Jacoby et al., 2004, 2005; Dua et al., 2006). Frequent underachievements in patients with epilepsy were demonstrated in many studies. (Verity and Ross, 1985; Britten et al., 1986; Sturniolo and Galletti, 1994). A significantly higher unemployment rate was found in PWE than among age- and gender-matched controls (Elwes et al., 1991). The higher unemployment, underemployment, or unskilled work rate, demonstrated amongst PWE by the RESt-1 Group, was in stark contrast with their better education (The RESt-1 Group, 2000). Unemployment and underemployment in people with epilepsy are related to a variety of factors, including associated neurological and neuropsychological problems (Rodin et al., 1972; Sillanpaa, 1994; Batzel et al., 1980). On the other hand, low socioeconomic status, as indexed by low education or lack of home ownership, was a risk factor for epilepsy in adults (Hesdorffer et al., 2005).
A. Guekht et al. As mentioned above, our study has certain limitations. Because of the huge territories involved and differences in geographic, ethnic, cultural practices of the study areas, some people with epilepsy, especially milder cases and elderly patients, may have been missed. Huge size and population of the country with 83 administrative territories and the impressive difference between them in many aspects, including substantial variations of population density between and within these territories, caused another limitation. As described in Section ‘‘Study population’’, we also had to take into consideration different types of communities, ethnic and other peculiarities, so the study was performed in 14 regions located in 6 administrative territories. We understand that our estimations of the prevalence of the epilepsy to the RF were rather rough. However, it was the first study that allowed to estimate the range of prevalence values in the RF and evaluate the difference between the Western and Eastern areas of the country. Further studies on epidemiology of epilepsy in specific regions in Russia will provide more detailed information
Conclusion The present study was the first to address prevalence and other basic epidemiologic data regarding epilepsy in the Russian Federation. The present investigation shows that the prevalence of epilepsy in the population ≥ 14 y.o. in Russia is consistent with results of the studies in adults in other European countries, although at lower end of the range. Age and gender trends are similar. The great majority of patients were on AED treatment, with almost equal proportion on monotherapy and polytherapy. Still, about one out of five patients with active epilepsy were not taking any AED. Special attention to improvement on epilepsy care, especially in the Eastern regions of the country, is required.
Acknowledgment We are grateful to our colleagues from the study regions of the Russian Federation: Balkhanova R.N., Boiko A.N., Golovanova I.V., Kabakov R.M., Kotov A.S., Kotov S.V., Pisova N.V., Perunova N.N., Shprach V.V., Spirin N.N., and Volkova L.I. for their invaluable collaboration.
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