Epidemiology of Amyotrophic Lateral Sclerosis

: We searched for full-text publications in Russian and English in the E-Library, PubMed, Springer, Clinical keys, Google Scholar databases, using keywords and combined word searches (amyotrophic lateral sclerosis - ALS, motor neuron disease, epidemiology, incidence, prevalence), for 2015 – 2020. In addition, the review included earlier publications of historical interest. Despite our comprehensive searches of these commonly used databases and search terms, it cannot be ex-cluded that some publications may have been missed. A total of 74 publications were analyzed, reflecting epidemiological studies of ALS in 168 countries. The incidence of ALS worldwide varies from 0.4 per 100,000 per year (Ecuador) to 9.45 per 100,000 per year (Japan, Oshima region). Prevalence - from 0.1 per 100,000 population (Somalia) to 42.1 per 100,000 population (Canada). This data depends on many factors, including the quality of the diagnosis and the health care system.


Introduction
Amyotrophic lateral sclerosis (ALS), or motor neurone disease (MND) is a severe progressive neurodegenerative disease that selectively affects the motor neurons of the spinal cord, brainstem and central motor neurons [1]. Usually the debut of ALS falls on 50-70 years of age [2]. Juvenile ALS is a rare form of the disease with a debut under the age of 25, occurring with variable phenotypic variants and rate of progression of the disease [3]. Clinically, the disease is characterized by weakness and atrophy of muscles in the extremities, fasciculations, dysarthria, dysphagia. There may be bulbar and pseudobulbar paralysis, lower paraparesis, central-peripheral paralysis, flaccid paralysis of the lower extremities, cognitive and mental disorders [4]. ALS is quite rare, but it progresses rapidly, causes disability and is characterized by high mortality [5]. The prognosis of the disease depends on the age of patients, the involvement of bulbar muscles, the rate of progression, but usually -it is unfavorable [6]. Timely diagnosis of ALS can reduce the rate of progression of the disease and improve the quality of life of patients at the initial stage. Due to the high mortality rate and the lack of specific therapy, ALS remains an urgent problem of modern neurology [7]. The study of the prevalence and incidence of ALS in different regions of Russia will help us to understand the cause of this disorder and develop a more accurate framework for identifying and combatting the disease .

Methods
We have searched for full-text publications in Russian and English in the E-Library, PubMed, Springer, Clinical keys, Google Scholar databases, using keywords and combined word searches (amyotrophic lateral sclerosis -ALS, motor neuron disease, epidemiology, morbidity, prevalence), for 2015-2020. In addition, earlier publications of historical interest were included in the review. Despite our comprehensive research of these frequently used databases and search terms, it cannot be ruled out that some publications may have been missed. A total of 34 publications reflecting epidemiological studies of ALS in 166 countries were analyzed.

Russia
We have analyzed 3 epidemiological studies conducted by Russian scientists and 1 study conducted in Russia as part of an international project. The variability of the incidence of ALS in Russia ranged from 1.25 per 100,000 per year (Moscow) [11] to 1.2 per 100,000 per year (Yakutia) [12]. The average incidence of ALS was 1.2 per 100,000 per year.

North America
In the North American region, epidemiological studies of ALS have been conducted in 3 countries (USA, Canada, Greenland). The incidence ranged from 1.4 per 100,000 per year (USA, state of California) [14] [17].
In Canada, the prevalence rate was 42.1 per 100,000 population [10]. We have not found any studies on the incidence of ALS.
In Greenland, the prevalence of ALS was 29.8 per 100,000 population [10]. We have not found any studies on the incidence of ALS.

South America
In the South American region, we found and analyzed epidemiological studies of In contrast, in Guadeloupe (Caribbean Islands) and Ecuador, the incidence rate was low (0.4 per 100,000 per year [8] and 0.93 per 100,000 per year [18], respectively).
The average prevalence of ALS was observed in the Republic of Panama (9.4 per 100,000 population), Guyana (9.0 per 100,000 population), the Dominican Republic (8.5 per 100,000 population), Puerto Rico (8.0 per 100,000 population), Trinidad and Tobago In the UK, the incidence of ALS was 1.66 per 100,000 per year, 1.97 per 100,000 among the population of European descent and 1.35 per 100,000 among the population of African descent (London) [20]. The prevalence rate in the UK was 34.5 per 100,000 population[10].
In Scotland, the incidence rate was 3.83 per 100,000 per year [9], the prevalence ranged from 7.61 to 7.81 per 100,000 population [9], the average level was 7.71 per 100,000 population.
In France, the incidence of ALS was 3.32 per 100,000 per year [21], and the prevalence  [24]. The average prevalence of ALS in the country was 9.37 per 100,000 population.

Eastern Europe
In Eastern Europe, we found and analyzed epidemiological studies of ALS in 13 [10], the average was 9.4 per 100,000 population.
In Turkey, the incidence of ALS varied from 1.3 per 100,000 per year (Antalya) [28] to 1.9 per 100,000 per year (Fraction) [29], the average incidence rate was 1.6 per 100,000 per year. The prevalence of ALS in Turkey varied from 4.6 per 100,000 population (Antalya) [29] to 7.3 per 100,000 population (Fraction) [30]. The average prevalence of ALS in the country was 5.9 per 100,000 population.
In China, the incidence of ALS was 1.65 per 100,000 per year [30]. The prevalence of ALS in China was 2.91 per 100,000 population [31]. In Korea, the incidence of ALS was 1.2 per 100,000 per year [27], and the prevalence ranged from 2.6 per 100,000 population The lowest prevalence rates of ALS were noted in Georgia (1.7 per 100,000 population) [10]. In Israel, the incidence rate was 1.8 per 100,000 per year [28], the prevalence rate was 8.1 per 100,000 population [28].

Middle East and Africa
In the Middle East and Africa region, we found and analyzed epidemiological studies In South Africa, the incidence rate of ALS was 1.09 per 100,000 per year [31], and the prevalence rate was 5.9 per 100,000 population [10].

Australia
In the Australia region, we found and analyzed epidemiological studies on ALS in 2 countries (Australia and New Zealand). The prevalence of ALS was high and ranged from 25.1 per 100,000 population (New Zealand) [10] to 30.3 per 100,000 population (Australia) [10], the average level was 27.7 per 100,000 population. We have not found any data on morbidity in this region.

Discussion
The analysis of epidemiological studies of ALS indicates that the neuromuscular disease in question is an urgent medical problem. The incidence and prevalence of ALS depends on many factors, including the quality of diagnosis and management of healthcare systems. Climatic, geographical, ethnic and racial risk factors of ALS affect epidemiological indicators, however, in general, we have not found significant epidemiological dynamics of ALS in the west-east direction and from north to south ( Figure 1). The problem of ALS requires improving approaches to early diagnosis, which is important for reducing the rate of progression of the disease and improving the quality of life of patients.

Conclusions
The epidemiology of ALS is being actively studied in Russia and worldwide.
According to our meta-analysis, the incidence and prevalence of ALS in the world is variable, which is probably genetically determined in some racial and ethnic groups of the population. ALS is a severe neurodegenerative disease which despite the low frequency of occurrence are characterized by high mortality. It is important to understand which