Amyotrophic Lateral Sclerosis and Frontotemporal

Degeneration

ISSN: (Print) (Online) Journal homepage: https://www.tandfonline.com/loi/iafd20

Amyotrophic lateral sclerosis in Antalya, Turkey. A

prospective study, 2016–2018

Hilmi Uysal , Parvin Taghiyeva , Mehtap Türkay , Fırat Köse & Mehmet
Aktekin

To cite this article: Hilmi Uysal , Parvin Taghiyeva , Mehtap Türkay , Fırat Köse &
Mehmet Aktekin (2020): Amyotrophic lateral sclerosis in Antalya, Turkey. A prospective
study, 2016–2018, Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, DOI:
10.1080/21678421.2020.1817089

To link to this article: https://doi.org/10.1080/21678421.2020.1817089

Published online: 12 Sep 2020.

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Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, 2020; 0: 1–7

REVIEW ARTICLE

Amyotrophic lateral sclerosis in Antalya, Turkey. A prospective

study, 2016–2018

HILMI UYSAL1 , PARVIN TAGHIYEVA1, MEHTAP TÜRKAY2, FIRAT KÖSE2 &

MEHMET AKTEKIN2
1
Department of Neurology, Faculty of Medicine, Akdeniz University, Antalya, Turkey, and 2Department of Public
Health, Faculty of Medicine, Akdeniz University, Antalya, Turkey

Abstract
Objective: The aim of the study is to find the prevalence and incidence of amyotrophic lateral sclerosis in Antalya and to
define patient characteristics.
Methods: The study represents five major districts in the Antalya metropolitan region, with a population of 1,286,943,
which is defined as the provincial center. In cooperation with the neurology departments of all hospitals and private
practices, existing cases were identified and new cases were recorded with continuous monitoring. Detailed demographic
and clinical features of each patient were recorded, Revised El-Escorial Criteria were used for diagnosis. Incidence and
prevalence rates are standardized by age based on USA 2016 population.
Results: Point prevalence rates of 2016, 2017 and 2018 are 3.7, 4.7 and 5.4 per hundred thousand, respectively.
Standardized prevalence rates for the US population are 5.5, 7.1 and 8.6 per hundred thousand in the same order. The
incidence rate in 2017 is 1.4 per hundred thousand, and 2018 is 1.2. Standardized incidence rates for the US population
are 2.1 and 1.8 per hundred thousand, respectively. About 75.6% of the cases were classified as definite, 11.0% prob-
able, 11.0% possible, 2.4% probable laboratory-supported. The male/female ratio is 2.0 for total cases and 2.8 for new
cases. The site of onset is spinal in 81.7% of patients and bulbar in 18.3%.
Conclusions: ALS rates detected in Antalya and the general features of the disease show similarities with European coun-
tries rather than Asian countries and comply with the literature.

Keywords: Amyotrophic lateral sclerosis, prospective study, incidence, point prevalence, period prevalence, Antalya, Turkey

Introduction hundred thousand (11). In a meta-analysis, the

Amyotrophic lateral sclerosis is characterized by
symptoms and signs of degeneration of the upper
and lower motor neurons, leading to progressive
weakness of the bulbar, limb, thoracic, and
abdominal muscles (1). The prognosis of the dis-
ease is poor and there is no cure. The links
between the symptoms of the disease and the
underlying causes were first described by Jean-
Martin Charcot (1825–1893) and the disease was
referred to as amyotrophic lateral sclerosis from
1874 onwards (2). Recent studies show that the
incidence of ALS ranges from 0.60 to 3.80 per
hundred thousand (3–10). The incidence rates
found in the community-based studies in the
European continent are between 1.70 and 2.43 per
incidence of ALS in Northern Europe was found
1.89 per hundred thousand. In the same study, the
rate was 1.75 in Southern Europe, 0.89 in East
Asia, 0.79 in South Asia, 1.19 in the Caribbean,
2.29 in New Zealand, and 1.59 in South America
(12). There are studies that have found that the
incidence has been increasing over the
years (3,5,10).
The prevalence of ALS ranges from 4.1 to 8.4
per hundred thousand (3–5,7,8,10,13). However,
there are some studies where prevalence is lower
or higher (14,15). The male/female ratio is usually
reported between 1 and 2 (3–5,8,10,13,16–20).
Male/female ratio was 1.78 in Turkey (10). The
average age of onset of the disease is between 51
and 66 (3–5,7,10,19,21–24). In community-based

Some of the data contained in this study were presented at the 55th National Neurology Congress in Antalya on 16–20 November 2019 and received an
award.
Correspondence: Mehmet Aktekin, Department of Public Health & Epidemiology, Akdeniz University, Antalya, Turkey. E-mail: maktekin@akdeniz.
edu.tr, mehmetaktekin1@gmail.com
(Received 23 June 2020; revised 19 August 2020; Accepted 23 August 2020)
ISSN 2167-8421 print/ISSN 2167-9223 online ß 2020 World Federation of Neurology on behalf of the Research Group on Motor Neuron Diseases
DOI: 10.1080/21678421.2020.1817089
2 H. Uysal et al.
Figure 1. Study area and location map.
studies, the age of onset is higher than in clinical-
based studies. In general, the diagnostic delay
ranges on average from 11 months to 14 months
(3,4,10) and from 9 to 12 months in median terms
(4,5,7,21,25,26). Various studies have shown that
patients have a spinal onset of between 58% and
82% (5,7,8,10,19,21,24–27). Bulbar onset is more
common in patients who develops the disease at
an older age (28–30). Recent studies report that
life span ranges from 24 to 50 months from the
onset of the symptoms (3,4,7,17,19,22–25,27,31).
Life expectancy is 24 months in Northern Europe
and 30 months in Western and Southern
Europe (32).
There is only one study examining the inci-
dence and prevalence of ALS in Turkey and
reflects the North East Turkey (10). The aim of
this study is to evaluate the incidence and preva-
lence of ALS in Antalya, a southern coastal city
of Turkey.
Materials and methods
The study was carried out in the central region of
the Antalya metropolitan area. Antalya city,
located in the south of Turkey (Figure 1). It has a
cosmopolitan population due to its huge tour-
ism potential.
The 2016 population of the metropolitan
region was 2,328,555. The population of the cen-
tral region, which covers the five major districts
where the research was conducted, was 1,286,943.
Table 1 shows the distribution of the population
by gender in the research region (33).
Akdeniz University and Antalya Training and
Research Hospitals located in the research area are
tertiary reference hospitals of the region. All neu-
rologists working in public and private hospitals
and private practices in the central region of
Antalya were contacted through the Clinical
Neurophysiology Association Antalya Branch, and
a short training was provided where cooperation
was established. Each neurologist was asked to fill
out a questionnaire about the ALS patients and
patients suspected of ALS, patients’ contact infor-
mation and the characteristics of their disease.
Patients diagnosed with ALS/MND with G12.2
code according to ICD-10 from the archives of all
hospitals were found and those residing in the
research area were included in the study. Patients
who were monitored in both hospital neuromuscu-
lar polyclinics and patients who were reported and
determined from the records were visited at home
by a nurse trained in ALS. For each patient, ‘the
translated patient follow-up form’ prepared by
‘ONWebDUALS – ONtology-based Web

Table 1. Population distribution of Antalya Central districts by
gender in 2016.
Districts Female Male Total population
Kepez 249,065 259,058 508,123
Muratpaşa 247,249 239,159 486,408
Konyaaltı 85,053 79,279 164,332
D€
oşemealtı 28,371 30,080 58,451
Aksu 34,080 35,549 69,629
Total 643,818 643,125 1,286,943
Database for Understanding Amyotrophic Lateral
Sclerosis’ supported by JPND – EU Joint
Programme Neurodegenerative Disease’ was filled
by researchers (34). Patients were selected accord-
ing to Revised El-Escorial criteria (35). According
to these criteria, patients diagnosed with definite,
probable, possible, and possible laboratory-sup-
ported ALS were included in the study. In add-
ition, primary lateral sclerosis (PLS) and
progressive bulbar palsy (PBP) patients were
included in the study. In contrast, patients diag-
nosed with hereditary spastic paraplegia (HSP)
and spinal muscular atrophy (SMA) were
excluded. Patients who met the criteria for inclu-
sion in the study were also required to live in the
research area for at least 1 year before diagnosis.
Those who could not fulfill this requirement were
excluded from research.
Neurology clinics of all hospitals in the region
and neurologists working in private practices
referred all cases of suspected ALS to Akdeniz
University School of Medicine Neuromuscular
outpatient clinic. New cases were detected with
this method and included in the follow-up pro-
gram. The number of eligible prevalent and inci-
dent cases is shown in Figure 2.
Initial involvement of the symptoms was classi-
fied as bulbar and spinal. It was analyzed whether
the onset was with symptoms of upper motor or
lower motor neurons.
Patients included in the study were followed-up
by the research team at the University Clinic every
three months and home visits every 6 months by
the trained nurse. Follow-ups were standardized
using patient follow-up forms. In these follow-ups,
Turkish version of Revised ALS Functional Rating
Scale (ALSFRS-R) was used to evaluate the prog-
nosis of the disease (36).
The study was approved by the local ethics
committee. Patients were included in the study
after obtaining written informed consent.
The crude prevalence of ALS was calculated as
the current frequency of living patients on 31
December 2016. New incidents that occurred
annually until 31 December 2017 and 31
December 2018 were used to calculate annual
crude incidence rates for 2017 and 2018. All
rates were standardized based on US 2016
Amyotrophic lateral sclerosis in Antalya, Turkey 3
population (37). Crude rates were recalculated as
age-specific and evaluated. Rates are presented
with 95% confidence intervals (CI), incidence
rates calculated as person-years (py).
Data were analyzed using SPSS for Windows
23.0 program (SPSS Inc., Chicago, IL). For
descriptive statistics, numerical and percentage val-
ues were used in categorical variables. Mean,
standard deviation, median, and minimum–maxi-
mum values were used in continuous variables.
Direct standardization method has been applied as
population standardization method. Chi-square
test was used to compare categorical variables. In
cases where parametric test assumptions are pro-
vided, T-test was used to compare continuous vari-
ables of two independent groups, and in cases
where parametric test assumptions were not pro-
vided, the Mann–Whitney U test was used. The
statistical significance level was accepted
as p < 0.05.
Results
As of 31 December 2016, 48 ALS patients were
identified. The crude point prevalence of ALS was
3.7 in a hundred thousand for 2016. The preva-
lence rate was 5.7 (5.64–5.80) per hundred thou-
sand when standardized according to the USA
2016 population. The demographic characteristics
of the patients are presented in Table 2. The
prevalence rate for the 70–74 age group was 13.3
(CI: 1.75 to 28.40) per hundred thousand and
42.9 (CI: 8.58 to 77.20) for the 75–79 age group.
Eighteen new cases of ALS were detected
between 31 December 2016 and 31 December
2017, and 16 cases between 31 December
2017–2018. The 2017 crude incidence rate was
1.4, and the 2018 crude incidence rate was 1.2 per
hundred thousand. When the rates were standar-
dized according to the 2016 US population, the
2017 standardized incidence rate was 2.1
(2.02–2.12), and the 2018 standardized incidence
rate was 2.0 (1.95–2.04) per hundred thousand.
The total number of new patients registered during
the 2016–2018 (2-year period) was 82. The preva-
lence and incidence rates for different periods are
shown in Table 3.
When 2017 and 2018 ALS overall incidences
were analyzed according to different demographic
characteristics, it was seen that the 2-year overall
incidence increased with age and had a tendency
to decrease by the age of 80 (Table 4). The 2-year
crude incidence rate for the 70–74 age group is
17.8, and 21.4 for the 75–79 age group per hun-
dred thousand. Incidence rate is significantly
higher in males than females.
It was seen that all of the patients (82 people)
included in the study, 55 were male (67.1%) and
27 were female (32.9%). Male/female ratio (M/F)
4 H. Uysal et al.

Figure 2. The number of eligible prevalent and incident cases.

Table 2. Distribution of 2016 ALS patients by age and gender.

Characteristics of the patients No of case (%)a Case per 100,000 population (prevalence) 95% CI
Age groups
<50 13 (27.1%) 1.3 0.59–2.01
50–59 11 (22.9%) 7.5 3.06–11.91
60–69 12 (25.0%) 13.5 5.84–21.06
70–79 9 (18.8%) 24.7 8.55–40.76
80 3 (6.2%) 21.4 2.81 to 45.51
Gender
Female 18 (37.5%) 2.8 1.51–4.09
Male 30 (62.5%) 4.7 2.99–6.33
Total 48 (100.0) 3.7 2.67–4.78

a
Column percentage.

Table 3. Crude and age standardized rates of ALS, Antalya, Turkey.

Year Rate Crude rate (per 100.000) Age-standardized rate (per 100.000) 95% CI
2016 Point Prevalence 3.7 5.7 5.64–5.80
2017 Point Prevalence 4.7 7.1 7.04–7.22
2018 Point Prevalence 5.4 8.6 8.54–8.74
2016–2018 Period Prevalence 6.4 9.8 9.70–9.91
2017 Incidence 1.4 2.1 2.02–2.12
2018 Incidence 1.2 2.0 1.95–2.04

was 2.0. When 2-year incident cases were exam-
ined, the M/F ratio rose to 2.8.
About 25.6% of 82 patients were under 50
years old, 19.5% were between 50 and 59 years
old, 30.5% were between 60 and 69 years old,
19.5% were 70–79 years old and 4.9% were above
80 years old. The mean age was 61.5 ± 13.1
(33–84). The mean age of male patients was
62.7 ± 12.0 and the mean age of female patients
was 59.2 ± 14.9. There was no statistical difference
between the age distribution of female and male
patients (p > 0.05).
The mean age at the onset of the first symp-
toms was 56.6 ± 14.1, 58.4 ± 12.0 in males and
52.9 ± 17.5 in females. The average age of diagno-
sis was 58.2 ± 14.1, 59.8 ± 12.3 in men and
54.8 ± 17.2 in women.
The delay in diagnosis after symptoms started
was 19.4 ± 27.4 months on average. One male
patient distorted the distribution with a very long

Table 4. Two-year crude incidence rates by age groups and gender.
Characteristics of the patients No. of case (%)a
Age groups
<50 8 (23.5%)
50–59 5 (14.7%)
60–69 13 (38.2%)
70–79 7 (20.6%)
80 1 (3.0%)
Gender
Female 9 (26.5%)
Male 25 (73.5%)
Total 34 (100.0%)
a
Column percentage.
b
Two year incidence.
diagnosis period (172.7 months). When this value
was excluded, the delay dropped to an average of
17.4 ± 21.5 months. Therefore, the median value
was taken into consideration and the delay in diag-
nosis was found to be 11.3 months in all patients.
There was no difference between men and women
in terms of diagnosis delay (p > 0.05). While the
median of delay in diagnosis in bulbar-onset
patients was 12.7 months, it was 9.6 in patients
with spinal onset (p > 0.05).
According to the El-Escorial criteria, 75.6% of
patients were classified as definite, 11.0% prob-
able, 11.0% possible, and 2.4% probable labora-
tory-supported.
About 6.2% of the cases were familial and
93.8% were sporadic. Four of the familial cases
were male and one was female. The median age of
these cases was 58.70, age of diagnosis was 56.51,
and the delay in diagnosis was 5.17 months. These
values for sporadic cases were 64.01, 60.45 and
11.75, respectively (p > 0.05). Each of the familial
cases had at least 1–9 patient relatives who were
previously diagnosed with ALS.
The site of onset was spinal in 81.7% of
patients and bulbar in 18.3% of patients. Bulbar
onset was 18.2% for males and 18.5% for females
(p > 0.05). The mean age of onset was 60.8 ± 10.5
in patients with bulbar onset, and 57.6 ± 14.7 in
patients with spinal onset (p > 0.05). The initial
finding of the disease was consistent with upper
motor neuron involvement in 29.3% of patients,
lower motor neuron involvement in 61.0% and
both in 9.8%. There was no difference between
upper or lower motor neuron involvement in terms
of gender, age of diagnosis, and delay in diagnosis
(p > 0.05). In patients with upper motor neuron
involvement at onset, survival was 24.7 ± 14.2
months after diagnosis, whereas in patients with
lower motor neuron involvement, survival was
73.1 ± 52.1 months (p < 0.05). In patients whose
disease begins with both motor neuron involve-
ment, the survival after diagnosis was the lowest
(14.2 ± 5.8 months).
Amyotrophic lateral sclerosis in Antalya, Turkey 5
Case per 100,000 population (incidence)b %95 CI
0.8 0.25–1.35
3.4 0.42–6.38
14.6 6.65–22.49
19.2 4.97–33.38
7.1 6.83 to 21.07
1.4 0.49–2.31
3.9 2.36–5.41
2.6 1.75–3.53
The average ALSFRS-R score at presentation
was 32.6 ± 12.3. A total number of 13 deaths
occurred in 2 years. Average life expectancy was
44.6 ± 44.2 and median was 37.2 months after
diagnosis. While life expectancy of patients with
bulbar onset was 27.4 ± 20.0 months, it is
55.3 ± 52.7 months in patients with spinal onset
(p > 0.05). The median survival time after diagno-
sis was 21.3 and 41.1 months, respectively. The
average age of death was 60.8 ± 14.1, which was
55.0 ± 21.2 for women and 63.4 ± 10.2 for men
(p > 0.05). The mean age of deaths in patients
with bulbar onset was 61.4 ± 12.0, and 60.5 ± 16.0
in patients with spinal onset (p > 0.05).
Discussion
This work is focused on the central region of
Antalya Metropolitan City that is located on the
south coast of Turkey. The crude incidence rates
are similar to those from countries outside
Northern Europe. However when standardized to
the US 2016 population, adjusted rates were 2.1
and 2.0 per hundred thousand for 2017 and 2018,
which are close to those in Northern Europe and
previously reported rates in the Thrace region.
Recent studies show that the prevalence of
ALS varies between 4.1% and 8.4% in the world
(5,7,10,13). In our study the prevalence was
within this range. The highest number of cases
were in the 60–69 age group, whereas the 2-year
incidence peaked in the 70–79 age group. Four of
the five familial cases were among the first
detected cases (prevalent cases), with a mean age
of 55.1 years and below the general average
(61.5). Our male to female ratio (2.0) was higher
than that reported in the Thrace region (1.8) and
may reflect an under ascertainment of females as
the proportion of spinal/bulbar patients was also
higher than in other studies.
This study has some limitations. Although the
unit where the study was conducted is a tertiary
6 H. Uysal et al.
reference clinic of ALS and is hosted to the
Clinical Neurophysiology Association, it is possible
that patients who passed away without a diagnosis
or patients who have directly received services
from other provinces or abroad without applying
to the health institutions in Antalya City were not
ascertained.
Turkey is a transition region among Asia,
Europe, and Africa. The information collected in
Turkey about ALS frequency will be helpful to be
understood easier of the genetic, climatic, environ-
mental, and socio-demographic characteristics of
the disease.
Ethical Approval
The research was examined and approved by
Akdeniz University Clinical Research Ethics
Committee (No. 2016/670).
Declaration of interest
The authors have no conflicting interests regarding
this manuscript.
ORCID
Hilmi Uysal http://orcid.org/0000-0002-
6063-377X
Mehmet Aktekin http://orcid.org/0000-0002-
0745-9194
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