Prevalence of amyotrophic lateral sclerosis in Latium region, Italy

Abstract Objective Prevalence estimate of amyotrophic lateral sclerosis (ALS) ranged between 1.1/100,000 and 11.2/100,000 inhabitants with different design of the study (prospective or retrospective) and sample size. The aim of this study is to conduct for the first time an estimate of the ALS prevalence in the Latium region. Materials and methods The study was performed in Latium, a region located in the center of Italy, with a population, as of January 1, 2016, of 5888.472 inhabitants. In this region, a network of 15 clinical centers (of which 4 referral ALS centers are located in Rome) and 10 local health authorities involved in the diagnosis and treatment of ALS patients has been identified. Each patient was classified according to the El Escorial revised criteria. Results The prevalence study in 2016 identified 353 ALS cases (200 males). By considering population aged >=20 years, the total crude prevalence rate resulted 7.33 (CI95% 6.59–8.14) × 100,000 and 8.75 and 6.05 in males and females, respectively. Age‐specific prevalence rates did not differ among males and females in the population aged less than 49 years. The difference emerged in population aged > 50 years. This type of diagnosis was recorded for 343 patients (11 missing). 68% of these patients have a definite diagnosis, 14% likely, 11% possible, and 12% defined as suspect. Conclusions The estimate of prevalence rates observed in this study is probably in line with the values reported in the literature for prospective prevalence studies.


INTRODUCTION
According to numerous studies, amyotrophic lateral sclerosis (ALS) incidence and prevalence widely varies between geographical areas worldwide, presuming that several factors (ancestral, genetic, environmental, and lifestyle) play an important role in the occurrence of the disease. However, methodological heterogeneity among studies determined through the years, conflicting results between European and non-European studies.  (Marin et al., 2017). This study, however, reported homogeneous rates between populations from Europe, North America, and New Zealand with a pooled ALS incidence of 1.81 (1.66-1.97)/100,000 PYFU. Conversely, no data regarding prevalence rates were reported (Marin et al., 2017 For example, in Italy, an ecological study investigated the possible role of latitude gradient in ALS risk, underlying that the ALS incidence rates of patients born in three Southern Italian regions were significantly higher than those of persons born in northern areas (Chiò et al., 1999).
Ethnicities also seem to play a role as several studies agreed that In East Asia, the peak of ALS incidence was estimated to be 74.3 years of age, which is in the same age range as that of Caucasians, but incidence rate was at 2. Recently, studies have attempted to estimate the projected increase of ALS cases between 2015 and 2040. ALS cases will increase from more than 222,000 to more than 376,000 globally, and this is probably due to aging populations mainly in developing countries where median age is slowly but progressively rising (Arthur et al., 2016). The aim of this paper is to conduct for the first time, an estimate of the ALS prevalence in the Latium region and to characterize the different clinical forms.

In 2014, the project "Elaboration of the Amyotrophic Lateral Sclerosis
Pathology Registry in the Latium Region" was funded by the Department of Social Policies of the Latium Region, with the aims to establish an ALS pathology registry in the Latium Region and to analyze demographic and clinical characteristics, and socio-welfare aspects of the patients.
The study was performed in Latium, a region situated in central Italy, with a land area of 17,232 km 2 . Administratively, Lazio is divided into four provinces (Frosinone, Latina, Rieti, and Viterbo) and one metropolitan (province-level) city (Rome).
As of January 1, 2016, the population of the study area was of 5,888,472 million (2,838,616 men; 3,049,856 women).
As a first step to conduct the study, we identified clinical centers For the present study, the research protocol was approved by the independent ethics committee of Italian National Institute of Health and an informed consent was signed by participants.

Statistical analysis
Population data on residents in Latium and in Italy as of January Distribution of site of disease onset in gender-and age-specific prevalence rates was also described.

RESULTS
The Population data, number of ALS cases, and crude and standardized prevalence rates by province are reported in Table 2. The Latium population was mainly resident in the province of Rome (about 73%), about 1 of 10 was resident in the province of Latina (10%) or Frosinone (9%), and few were resident in Viterbo (5%) or Rieti (3%). The majority of ALS Latium patients was resident in Rome (n = 290, 82.2%), some cases were resident in Latina (n = 23, 6.5%), Frosinone (n = 23, 6.5%), and Viterbo (n = 14, 4.0%), and very few cases were resident in Rieti (n = 3, 0.8%). The crude prevalence rate showed differences by province (see Table 2), with a very low rate in the province of Rieti. Standardized prevalence ratios suggested that prevalence of ALS in Lazio provinces did not differ from European estimates, except for the province of Rieti (see in Table 2), suggesting that the lower prevalence rate observed in Rieti was not fully explained by age distribution.

DISCUSSION
The estimate of prevalence rates observed in this study is probably in  In our study, the ALS with bulbar onset was more frequent in females than in males in advanced age classes, while age-specific prevalence rates for spinal onset were higher in males in all age classes (see Figure 1). This different pattern may be relevant from an etiological prospective. In a previous case-control study performed in the province of Rome, some of the hypothesized risk factors (smoke, occupational exposure, and head injures) for ALS have been found positively associated with different patterns between bulbar and spinal ALS (Binazzi et al., 2009). However, it is reported that the incidence of ALS varied across provinces according to age, sex, and site of onset (Beghi et al., 2007).
This complex pathology is probably due to an interaction between genetic and environmental factors that must yet be identified (