- Email: [email protected]
Incidence and prevalence of multiple sclerosis in southeastern Iran
Clinical Neurology and Neurosurgery 115 (2013) 304–308
Contents lists available at SciVerse ScienceDirect
Clinical Neurology and Neurosurgery journal homepage: www.elsevier.com/locate/clineuro
Incidence and prevalence of multiple sclerosis in southeastern Iran Ali Moghtaderi ∗ , Forough Rakhshanizadeh, Shahryar Shahraki-Ibrahimi Neurology Department, Zahedan University of Medical Sciences, Zahedan, Iran
a r t i c l e
i n f o
Article history: Received 12 January 2011 Received in revised form 23 May 2012 Accepted 25 May 2012 Available online 18 June 2012 Keywords: Multiple sclerosis Prevalence Incidence Iran
a b s t r a c t Background: Based on data available, Iran is located in a low risk area for multiple sclerosis (MS). The objective of the current study is to determine the age and sex adjusted prevalence and incidence of MS in southeastern Iran. Methods: This cross-sectional case register study was conducted from January to August 2010. Considering that MS affects people aged between 16 and 50 years, we intended to find the incidence and prevalence of MS during this age range. Since all cases in this area are referred to our university hospital for confirmation of diagnosis, misdiagnosis is rare. Population data, based on the censuses carried out in 1996 and 2006, were obtained from the Iranian Bureau of Statistics to determine the number of people at risk. Results: Totally 206 patients were identified according to the McDonald criteria. In 2009 the age-adjusted prevalence and incidence rates of MS for 16–50 year-old adults were 13.96 and 2.67 per 100,000 persons, respectively. Based on those values; the female to male ratio was 2.18. Between 2006 and 2009, the incidence rates increased 2.4 and 2.7 times in women and men, respectively. In 2009, the prevalence rates among the age ranges of <15, 16–35, 36–50 and ≥51 years were 1.44, 14.34, 12.24 and 1.45 per 100,000 persons, respectively, and the relapsing-remitting type of MS was the most prevalent form (65.8%). Conclusion: According to the Kurtzke geographical distribution, the authors conclude that the prevalence of MS in southeastern Iran is in the intermediate range, and the incidence rate is showing a faster growth rate, compared to previous years. © 2012 Elsevier B.V. All rights reserved.
1. Introduction Multiple sclerosis (MS) is an inflammatory demyelinating disease of unknown origin. Until recently, tropical and subtropical regions such as Iran have been classified as areas of low MS prevalence [1,2]. Although several studies have been done worldwide to clarify the epidemiological patterns of the disease, researchers have not yet been able to ascertain the accurate geographical distribution, or the precise prevalence and incidence of MS. Based on earlier studies, Kurtzke [3,4] proposed a map and divided the world into three regions of: (1) high (≥30/100,000); (2) intermediate (between 5 and 25/100,000, mostly between 10 and 15/100,000); and (3) low risk for MS (<5/100,000) [5]. To date, some investigations have estimated the prevalence of MS as being less than 10/100,000 people in countries located in Asia and Africa. Recent studies have suggested that the direct relationship between the prevalence and latitude is no longer valid and has been replaced by other important risk factors such as vitamin D hypovitaminosis, genetics and early viral
∗ Corresponding author at: Neurology Department, Imam-Ali Teaching Hospital, Zahedan, Iran. Tel.: +98 541 3218016; fax: +98 541 3218848. E-mail addresses: [email protected], [email protected] (A. Moghtaderi). 0303-8467/$ – see front matter © 2012 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.clineuro.2012.05.032
infections, all of which play important roles in the development of the disease [6,7]. The distribution of the prevalence and incidence of MS is more complex and uneven than previously supposed and little is known about the wide variations among different ethnic groups in any country and areas at the same latitudes. The different reasons proposed for this inequality in the reported distribution of patients, are accuracy of case ascertainment, definition of the onsetadjusted prevalence, the diagnostic criteria used and the failure to distinguish between the MRI and clinical characteristics of MS and disseminated encephalomyelitits (DEM) [8]. According to the Kurtzke map, Iran is located in the low risk area (<5/100,000) [5]; this was confirmed by some earlier studies in Iran [9]; however the increase in the prevalence of MS was not clear [10,11]. There are few studies that clarify the epidemiologic distribution of MS in Iran. The highest prevalence rate has been reported from Isfahan, a province in central Iran [12]. MS is a chronic disease with a heavy economic and social burden leading to severe disability and social dependence. The objective of this study was to determine the crude and age-adjusted incidence and prevalence of MS during the last four years in Sistan & Balouchestan, a province in southeastern Iran. The authors should point out that this research is a starting point for determining the burden of MS in the largest province of Iran and it will be helpful for future epidemiological studies.
A. Moghtaderi et al. / Clinical Neurology and Neurosurgery 115 (2013) 304–308
305
Fig. 1. Provinces in Iran in which incidence and prevalence of multiple sclerosis have been studied.
2. Methods 2.1. Patient selection This study was conducted in the Sistan & Balouchestan province, which is the largest province of Iran, bordering Afghanistan and Pakistan (Fig. 1). It is located in southeastern Iran (29◦ N and 60◦ E), and has the highest birth rate in the country (over 3%), with a population of over 2.5 million and a high proportion of young adults (45.7%), aged between 16 and 50. The population consists of two ethnic “Fars” groups, who live mainly in the northern part of the province and the “Balouches”, residing mainly in the southern part. The province is in the subtropical/tropical region with dry and hot weather in summer and dry-cold weather in winter. The study population includes all residents living in this area since the past 15 years, except for Afghan refugees. The socioeconomic status of the inhabitants is more or less similar to that of other parts of the country. Health services are provided by private, governmental and academic faculty neurologists affiliated to teaching hospitals. Because of the high prices of different drugs, especially interferons, prescribed as first line of treatment for MS, all cases are referred to our university hospital for confirmation of diagnosis, following which the patient, once reassured, can begin the treatment prescribed. All data had been archived, therefore gathering it was easy for us, except for those patients who had a diagnosis confirmed elsewhere in the country or had migrated to this province for different reasons. The authors conducted a cross-sectional case register study from January to August 2010. The diagnosis was based on clinical findings, brain and spinal cord MRI studies, CSF analyses and visual evoked potential (VEP), according to the McDonald criteria and its revision [13,14]. We tested all patients for collagen-vascular
diseases and had antinuclear antibody (ANA), ds-DNA and antiphospholipid antibody laboratory tests done. Routine laboratory examinations, visual evoked potential, and CSF analyses were performed and brain and cervical cord MRIs were taken in almost all patients; some did not give us consent to perform a lumbar puncture and hence CSF analyses were not carried out for these patients. All cases with clinically definite MS, Clinically Isolated Syndrome (CIS) and Neuromyelitis Optica (NMO; Devic’s disease) were enrolled for the study. The diagnosis of NMO was based on the medical history of patients (development of optic neuritis and presence of extensive demyelinating lesions in the cervical spinal cord as well as the results of visual evoked potential. We could not measure aquaporin-4 antibody in the CSF in our lab. Using our database, we could trace patients who had left the province or had died and therefore we included them in the study to calculate the actual incidence rate if they were born in this region or had lived there since the past 10 years; however they were excluded for calculation of the prevalence rate. We had also excluded patients who had recently moved to the province for various reasons. Since MS affects people, aged 16–50 years, we also intended to find the incidence and prevalence for this age range. Finally we calculated prevalence during the study years in the total population and its subcategories according to their age range and gender. We did not have any patient in whom the disease had begun after the age of 50. Demographic information, including name, parents’ name, age, marital status, and education were obtained from the patients or their relatives. We also collected other relevant clinical data, such as the first neurological episode compatible with MS disease (type and year), CSF and MRI findings, occupation and place of birth and residence The Iranian Bureau of Statistics regularly estimates the average annual population, based on the 1996 and 2006 census data. To calculate the prevalence and incidence, we used the above
306
A. Moghtaderi et al. / Clinical Neurology and Neurosurgery 115 (2013) 304–308
mentioned data to find the population at risk (denominator). This study was approved by the Institutional Ethics Committee of the Zahedan University of Medical Sciences. 2.2. Statistical analysis MS prevalence and incidence rates per 100,000 persons were calculated according to gender and age groups between the years 2006 and 2009. We used SPSS software for Windows, Version 15 (SPSS Inc., Chicago, IL, USA) to calculate median, arithmetic mean, and standard deviation for different variables. Comparisons were accepted as statistically significant at the conventional p-value of less than 0.05. Fig. 2. Number of new cases of multiple sclerosis during the last 10 years.
3. Results After exclusion of 31 patients from the study group, a total of 206 patients were identified during the last 15 years according to the McDonald criteria. In 2009, 188 patients were aged between 16 and 50 years and 36 patients were new cases. The total population at risk (aged 16–50 years) in the same year was 1,346,367 persons in the province. Therefore, in the year 2009, prevalence and incidence rates were 13.96 and 2.67 per 100,000 persons; corresponding values for the last three years are presented in Table 1. Table 2 shows the incidence and prevalence of MS diseases, according to the age range and sex, in the population at risk. Based on these values, female to male ratios were between 2.22 (in 2006) and 2.18 (in 2009). In the above mentioned years the incidence rates increased 2.4 and 2.7 times in women and men, respectively. Table 3 shows total prevalence rate according to sex. Overall prevalence and incidence rates increased about 1.5 and 2.4 times in women and 1.52 and 2.7 times in men, respectively. In 2009, 18 patients (8.73%) were under 16 or over 51 years old, most being between 16 and 35. In 2009, the prevalence rate in the <15, 16–35, 36–50 and ≥51-year age groups were 1.44, 14.34, 12.24 and 1.45 per 100,000 persons, respectively. Total incidence rates were 0.59, 0.84, 1.11 and 1.47 per 100,000 people in the years 2006–2009, respectively, while the total prevalence rates in these years were 5.14, 5.75, 6.58 and 7.69 per 100,000 individuals, respectively (Table 4). Mean ages for the first symptom were 28.2 ± 9.8 and 26.5 ± 8.2 years for men and women, respectively. Mean time for the diagnosis after the first presentation was 1.7 ± 1.1 years. The relapsing-remitting type of the MS was the most prevalent form
(65.8%), followed by the secondary progressive (20%), primary progressive (6.7%) and the progressive-relapsing (2%) types. Eight cases (5.4%) had Devic’s disease. Mean scores for EDSS scores for men and women were 3.62 ± 2.3 and 2.70 ± 2.1, respectively; this mean score for patients, aged between 16 and 35 years, was 2.82 ± 2.3 and for patients aged 36–50 years was 3.42 ± 2.9. Numbness and other sensory disturbances, except for visual loss, were the most frequent presenting manifestations (39.8%) followed by motor dysfunction (28.6%) and optic neuritis (28.2%). Twenty-two percent of the cases had more than one symptom at the first presentation. Thirteen cases (6.2%) had positive family history in their first-degree relatives and one couple had conjugal MS, indicating that the husband had been affected by the disease after marriage. Eighty-six percent of subjects were married and only 29% were of Balouch origin. Fig. 2 shows the increasing number of the new cases during the last ten years. 4. Discussion We found age-adjusted and total prevalence rates of 13.96 and 7.69 per 100,000 persons in southeastern Iran in 2009. The incidence rate is increasing rapidly, being 3.62 for women, 1.75 for men and 2.67 per 100,000 persons totally in the last year of the study. Located in a tropical/subtropical region, this province of Iran can be classified as an intermediate area for MS prevalence. To the best of our knowledge this is the first age-adjusted report of the incidence rate of MS in an Iranian population.
Table 1 Age-adjusted prevalence and incidence of MS during 2006–2009 in Sistan & Balouchestan province, Iran.
2006 2007 2008 2009
Population at risk (16–50 years)
Total MS patients
New MS patients
Prevalence per 100,000 persons
Incidence per 100,000 persons
1,215,874 1,259,281 1,302,096 1,346,367
113 129 154 188
13 19 26 36
9.29 10.24 11.82 13.96
1.07 1.50 1.99 2.67
Table 2 Age-adjusted prevalence and incidence of MS during 2006–2009 according to sex in Sistan & Balouchestan province, Iran. Population at risk
2006 2007 2008 2009
Women (16–50 years)
Men (16–50 years)
599,559 619,944 641,021 662,816
616,314 639,336 661,074 683,551
Total MS patients (F/M)
New MS patients (F/M)
Prevalence per 100,000 persons (F/M)
Incidence per 100,000 persons (F/M)
78/35 89/40 106/48 129/59
9/4 13/6 17/9 24/12
13.00/5.67 14.35/6.25 16.53/7.26 19.46/8.63
1.50/0.64 2.09/0.94 2.65/1.36 3.62/1.75
A. Moghtaderi et al. / Clinical Neurology and Neurosurgery 115 (2013) 304–308
307
Table 3 Total prevalence and incidence of MS for all ages during 2006–2009 according to sex in Sistan & Balouchestan province, Iran. Population at risk
2006 2007 2008 2009
Women
Men
1,178,813 1,218,999 1,260,335 1,303,185
1,226,928 1,268,643 1,311,777 1,356,376
Total MS patients (F/M)
New MS patients (F/M)
Prevalence persons (F/M)
Incidence persons (F/M)
84/39 97/45 114/56 138/68
9/4 13/6 17/9 24/12
7.13/3.18 7.95/3.54 9.05/4.27 10.59/5.01
0.76/0.32 1.06/0.47 1.35/0.68 1.84/0.88
Table 4 Total prevalence and incidence of MS during 2006–2009 in Sistan & Balouchestan province, Iran.
2006 2007 2008 2009
Total population
Total MS patients
Total prevalence per 100,000 persons
Total incidence per 100,000 persons
2,198,443 2,243,478 2,340,425 2,444,733
113 129 154 188
5.14 5.75 6.58 7.69
0.59 0.84 1.11 1.47
Little is known about the epidemiology of MS in Iran. Wadia and Bhati in 1990 found an intermediate prevalence of MS among the Iranian immigrant (Zoroastrians) in India during the 7th and 10th centuries AD; the age-adjusted prevalence in Bombay was 24/100,000 and it was higher than the usual low risk populations of Asian and African countries [15]. Two years earlier, in a door to door survey conducted among Iranian immigrants (Parsis) living in colonies in Bombay, the prevalence rate of clinically definite MS was reported to be 21/100,000 [16]. Ale-Yasin and his colleagues [9] have reported the demographic and clinical characteristics of 318 patients living in Tehran, Iran; although the study was not population based, they estimated a prevalence of 4/100,000. In their study, sensory impairment was the most frequent presenting symptom, followed by visual impairment. The true frequency of optic neuritis and any case of Devic’s disease have not been reported. In another six-month study, published in a local Persian journal the point prevalence rate among MS patients living in northern Iran (Mazandaran) had been reported to be 20.1/100,000 [17]; the study was not population-based and 582 MS patients from one registry were used to calculate the prevalence rate; the female to male ratio was 2.6 and the most frequent reported symptom was visual disturbances. The only report from the southwestern province of Iran (Khuzestan) showed a crude prevalence rate of 14.04/100,000 [11]; in this study the prevalence rate for a resident Arab population was much lower compared to the inhabitants of Persian origin (8.58 vs. 16.16/100,000). According to the high rate of NMO in our patients it seems that the “Asian type” of MS with optico-spinal involvement, transverse myelitis and severe visual loss is more common in this area. However this needs to be further investigated with more cases. The first Iranian population-based study was done in central province of Isfahan which revealed a prevalence rate of 35.5/100,000 in 2005 [12]. The same center reported a crude prevalence rate of 43.8/100,000 for a total patient population of 1718 after one year [18]. In this study the prevalence rate in women was 3.4 times more than that of men (69.6 vs. 19.2). There are probably some reasons that the reported prevalence rate was higher than other parts of the country; however, no one has yet looked at the more important question that not all the reported patients were visited by the researchers and most of them were enrolled into the study based on the discharge letter issued by neurologists. Sometimes it is difficult to differentiate between MS and disseminated encephalomyelitis (DEM) because McDonald diagnostic criteria are purely quantitative and lack any qualitative descriptive features.
The appearance of plaques is more important than their number to differentiate MS from recurrent DEM [8]; this may increase the rate of misdiagnosis based on the McDonald criteria. Prevalence studies have traditionally focused on a geographical area and population group. It seems logical that the researcher counts only patients whose disease started after they had been living for a longtime in the region, otherwise it may show an abnormally high prevalence rate [19]. Isfahan is the second largest city of Iran. Due to its location in the central part of country, many people from most parts of Iran move there, living with their families, in search of jobs, and to have access to sophisticated medical facilities: due to the chronicity of multiple sclerosis and the constant need for treatment and access to an expert neurologist, they may remain in the city for a long time. It was not reported whether those patients who belonged to immigrated population had been excluded from the study or not. Therefore, the population at risk (denominator) is fixed but the number of patients increased. We suppose that this is the most important reason for the high prevalence rate reported in central parts of Iran. However, based on the theory that MS may be caused by an infection, the high number of patients may be due to an epidemic infection during the last 20 years, which has now presented itself as clinical neurologic multiple sclerosis (CNMS) [1,7,20]. Confirming or refuting these theories needs more accurate studies. In a newly published article, Elhami et al. [21] reported that the MS incidence in 2008 was 2.93/100,000 population in Tehran, Iran. Middle-Eastern countries located in Asia and a part of Africa are classified as the low risk areas [22,23] but other studies revealed that the worldwide prevalence of MS is much higher than those previously reported [24]. It seems that the distribution of MS is very uneven due to great differences among regions in the same latitude and different parts of the same countries [25]. In Kuwait the reported crude prevalence has increased from 10/100,000 in 1980 [26] to 14.7/100,000 in 2000 [27]. The prevalence among a pure Kuwaitis population was 11.02/100,000 in 1993 and increased to 31.15/100,000 in 2000 [28]. The reported prevalence in Jordan was 7/100,000 [29] but recently it has been reported to be 32/100,000 in one study [30] and 39 per 100,000 in another [31]. In Saudi Arabia, the prevalence rate of MS increased from 8/100,000 in 1977 [32] to 25/100,000 in 1998 [33]. However, we cannot draw a definite conclusion about the prevalence of MS in Middle-Eastern countries due to methodological inconsistencies among published studies. Nevertheless, we can conclude that the prevalence in those countries is escalating, and it depends on the specific population and environment of the study [28].
308
A. Moghtaderi et al. / Clinical Neurology and Neurosurgery 115 (2013) 304–308
Our study has some limitations which may to a slight extent affect the calculation of incidence and prevalence of the disease. Despite the fact that the authors have tried to collect complete data from all patients, there were some who had moved to other major central cities, seeking better health care, affecting possibly the true incidence and prevalence of the disease. It needs to be mentioned that a meticulous door-to-door study would show higher number of patients in this area, but because of population dispersion in an extensive area, such a study is very difficult and virtually impossible. Although our study does report figures regarding MS prevalence, further studies are needed to answer critical questions regarding factors that impact MS prevalence. Based on their findings, the authors conclude that the prevalence of MS in southeastern Iran is in the intermediate range in the population at risk, and that the incidence rate is growing faster than previous years. More follow up studies are needed to understand and analyze the patterns of the disease in this region. Acknowledgements This paper was based on the MD thesis of Dr. F. Rakhshanizadeh and was supported financially by the Dean for Research Affairs at the Zahedan University of Medical Sciences. The authors would like to acknowledge Ms. Nilufar Shiva and Dr. Mohsen Javadzadeh for language editing of the manuscript. References [1] Kurtzke JF. Epidemiologic evidence for multiple sclerosis as an infection. Clinical Microbiology Reviews 1993;6(October (4)):382–427. [2] Turk Boru U, Alp R, Sur H, Gul L. Prevalence of multiple sclerosis door-to-door survey in Maltepe, Istanbul, Turkey. Neuroepidemiology 2006;27(1):17–21. [3] Kurtzke JF. Epidemiology of multiple sclerosis. Does this really point toward an etiology? Lectio Doctoralis. Neurological Sciences 2000;21(December (6)):383–403. [4] Kurtzke JF. Epidemiology and multiple sclerosis. Revista de Neurologia 2002;35(December (12)):1177. [5] Kurtzke JF. A reassessment of the distribution of multiple sclerosis. Part one. Acta Neurologica Scandinavica 1975;51(February (2)):110–36. [6] Poser CM. Notes on the epidemiology of multiple sclerosis. Journal of the Formosan Medical Association 1995;94(June (6)):300–8. [7] Kurtzke JF. Epidemiology and etiology of multiple sclerosis. Physical Medicine and Rehabilitation Clinics of North America 2005;16(May (2)):327–49. [8] Poser CM, Brinar VV. The accuracy of prevalence rates of multiple sclerosis: a critical review. Neuroepidemiology 2007;29(3–4):150–5. [9] Ale-Yasin H, Sarai A, Alaeddini F, Ansarian E, Lotfi J, Sanati MH. Multiple slerosis: a study of 318 cases. Archives of Internal Medicine 2002;5(1):24–7. [10] Ghandehari K, Riasi HR, Nourian A, Boroumand AR. Prevalence of multiple sclerosis in north east of Iran. Multiple Sclerosis 2010;16(December (12)):1525–6. [11] Sharaffadinzadeh N, Majdinasab N, Kashipazha D, Shalbafan B. Multiple sclerosis in Khuzestan, Iran. In: Sixth international Iranian congress on MS. Tabriz, Iran: Tabriz Neuroscience Research Center; 2009. p. 9.
[12] Etemadifar M, Janghorbani M, Shaygannejad V, Ashtari F. Prevalence of multiple sclerosis in Isfahan, Iran. Neuroepidemiology 2006;27(1):39–44. [13] McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD, et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Annals of Neurology 2001;50(July (1)):121–7. [14] Polman CH, Reingold SC, Edan G, Filippi M, Hartung HP, Kappos L, et al. Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald Criteria”. Annals of Neurology 2005;58(December (6)):840–6. [15] Wadia NH, Bhatia K. Multiple sclerosis is prevalent in the Zoroastrians (Parsis) of India. Annals of Neurology 1990;28(August (2)):177–9. [16] Bharucha NE, Bharucha EP, Wadia NH, Singhal BS, Bharucha AE, Bhise AV, et al. Prevalence of multiple sclerosis in the Parsis of Bombay. Neurology 1988;38(May (5)):727–9. [17] Abedini M, Habibi-Saravi R, Zarvani A, Farahmand M. Epidemiology of multiple sclerosis in Mazandran province in 2007. Journal of Mazandaran University of Medical Sciences 2008;18(66):82–7 (Persian). [18] Saadatnia M, Etemadifar M, Maghzi AH. Multiple sclerosis in Isfahan, Iran. International Review of Neurobiology 2007;78(4):357–75. [19] Mayr WT, Pittock SJ, McClelland RL, Jorgensen NW, Noseworthy JH, Rodriguez M. Incidence and prevalence of multiple sclerosis in Olmsted County, Minnesota, 1985–2000. Neurology 2003;61(November (10)):1373–7. [20] Kurtzke JF, Hyllested K. Multiple sclerosis in the Faroe Islands and the lack of protection by exposure in infancy. Neuroepidemiology 1992;11(2):90–9. [21] Elhami SR, Mohammad K, Sahraian MA, Eftekhar H. A 20-year incidence trend (1989–2008) and point prevalence (March 20, 2009) of multiple sclerosis in Tehran, Iran: a population-based study. Neuroepidemiology 2011;36(3):141–7. [22] Kurtzke JF. Epidemiologic contributions to multiple sclerosis: an overview. Neurology 1980;30(July (7 Pt 2)):61–79. [23] Poser CM. The epidemiology of multiple sclerosis: a general overview. Annals of Neurology 1994;36(December (Suppl. 2)):S180–93. [24] Rosati G. Descriptive epidemiology of multiple sclerosis in Europe in the 1980s: a critical overview. Annals of Neurology 1994;36(December (Suppl. 2)):S164–74. [25] Rosati G. The prevalence of multiple sclerosis in the world: an update. Neurological Sciences 2001;22(April (2)):117–39. [26] Al-Din AS, Khogali M, Poser CM, Al-Nassar KE, Shakir R, Hussain J, et al. Epidemiology of multiple sclerosis in Arabs in Kuwait: a comparative study between Kuwaitis and Palestinians. Journal of the Neurological Sciences 1990;100(December (1–2)):137–41. [27] Alshubaili AF, Alramzy K, Ayyad YM, Gerish Y. Epidemiology of multiple sclerosis in Kuwait: new trends in incidence and prevalence. European Neurology 2005;53(3):125–31. [28] Al-Hashel J, Besterman AD, Wolfson C. The prevalence of multiple sclerosis in the Middle East. Neuroepidemiology 2008;31(2):129–37. [29] Kurdi A, Ayesh I, Abdallat A, Maayta U. Different B lymphocyte alloantigens associated with multiple sclerosis in Arabs and North Europeans. Lancet 1977;1(May (8022)):1123–5. [30] Al-Din AS, El-Khateeb M, Kurdi A, Mubaidin A, Wriekat A, Al-Shehab A, et al. Multiple sclerosis in Arabs in Jordan. Journal of the Neurological Sciences 1995;131(August (2)):144–9. [31] El-Salem K, Al-Shimmery E, Horany K, Al-Refai A, Al-Hayk K, Khader Y. Multiple sclerosis in Jordan: a clinical and epidemiological study. Journal of Neurology 2006;253(September (9)):1210–6. [32] Yaqub BA, Daif AK. Multiple sclerosis in Saudi Arabia. Neurology 1988;38(April (4)):621–3. [33] Daif AK, Al-Rajeh S, Awada A, Al Bunyan M, Ogunniyi A, AbdulJabar M, et al. Pattern of presentation of multiple sclerosis in Saudi Arabia: analysis based on clinical and paraclinical features. European Neurology 1998;39(3):182–6.
Contents lists available at SciVerse ScienceDirect
Clinical Neurology and Neurosurgery journal homepage: www.elsevier.com/locate/clineuro
Incidence and prevalence of multiple sclerosis in southeastern Iran Ali Moghtaderi ∗ , Forough Rakhshanizadeh, Shahryar Shahraki-Ibrahimi Neurology Department, Zahedan University of Medical Sciences, Zahedan, Iran
a r t i c l e
i n f o
Article history: Received 12 January 2011 Received in revised form 23 May 2012 Accepted 25 May 2012 Available online 18 June 2012 Keywords: Multiple sclerosis Prevalence Incidence Iran
a b s t r a c t Background: Based on data available, Iran is located in a low risk area for multiple sclerosis (MS). The objective of the current study is to determine the age and sex adjusted prevalence and incidence of MS in southeastern Iran. Methods: This cross-sectional case register study was conducted from January to August 2010. Considering that MS affects people aged between 16 and 50 years, we intended to find the incidence and prevalence of MS during this age range. Since all cases in this area are referred to our university hospital for confirmation of diagnosis, misdiagnosis is rare. Population data, based on the censuses carried out in 1996 and 2006, were obtained from the Iranian Bureau of Statistics to determine the number of people at risk. Results: Totally 206 patients were identified according to the McDonald criteria. In 2009 the age-adjusted prevalence and incidence rates of MS for 16–50 year-old adults were 13.96 and 2.67 per 100,000 persons, respectively. Based on those values; the female to male ratio was 2.18. Between 2006 and 2009, the incidence rates increased 2.4 and 2.7 times in women and men, respectively. In 2009, the prevalence rates among the age ranges of <15, 16–35, 36–50 and ≥51 years were 1.44, 14.34, 12.24 and 1.45 per 100,000 persons, respectively, and the relapsing-remitting type of MS was the most prevalent form (65.8%). Conclusion: According to the Kurtzke geographical distribution, the authors conclude that the prevalence of MS in southeastern Iran is in the intermediate range, and the incidence rate is showing a faster growth rate, compared to previous years. © 2012 Elsevier B.V. All rights reserved.
1. Introduction Multiple sclerosis (MS) is an inflammatory demyelinating disease of unknown origin. Until recently, tropical and subtropical regions such as Iran have been classified as areas of low MS prevalence [1,2]. Although several studies have been done worldwide to clarify the epidemiological patterns of the disease, researchers have not yet been able to ascertain the accurate geographical distribution, or the precise prevalence and incidence of MS. Based on earlier studies, Kurtzke [3,4] proposed a map and divided the world into three regions of: (1) high (≥30/100,000); (2) intermediate (between 5 and 25/100,000, mostly between 10 and 15/100,000); and (3) low risk for MS (<5/100,000) [5]. To date, some investigations have estimated the prevalence of MS as being less than 10/100,000 people in countries located in Asia and Africa. Recent studies have suggested that the direct relationship between the prevalence and latitude is no longer valid and has been replaced by other important risk factors such as vitamin D hypovitaminosis, genetics and early viral
∗ Corresponding author at: Neurology Department, Imam-Ali Teaching Hospital, Zahedan, Iran. Tel.: +98 541 3218016; fax: +98 541 3218848. E-mail addresses: [email protected], [email protected] (A. Moghtaderi). 0303-8467/$ – see front matter © 2012 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.clineuro.2012.05.032
infections, all of which play important roles in the development of the disease [6,7]. The distribution of the prevalence and incidence of MS is more complex and uneven than previously supposed and little is known about the wide variations among different ethnic groups in any country and areas at the same latitudes. The different reasons proposed for this inequality in the reported distribution of patients, are accuracy of case ascertainment, definition of the onsetadjusted prevalence, the diagnostic criteria used and the failure to distinguish between the MRI and clinical characteristics of MS and disseminated encephalomyelitits (DEM) [8]. According to the Kurtzke map, Iran is located in the low risk area (<5/100,000) [5]; this was confirmed by some earlier studies in Iran [9]; however the increase in the prevalence of MS was not clear [10,11]. There are few studies that clarify the epidemiologic distribution of MS in Iran. The highest prevalence rate has been reported from Isfahan, a province in central Iran [12]. MS is a chronic disease with a heavy economic and social burden leading to severe disability and social dependence. The objective of this study was to determine the crude and age-adjusted incidence and prevalence of MS during the last four years in Sistan & Balouchestan, a province in southeastern Iran. The authors should point out that this research is a starting point for determining the burden of MS in the largest province of Iran and it will be helpful for future epidemiological studies.
A. Moghtaderi et al. / Clinical Neurology and Neurosurgery 115 (2013) 304–308
305
Fig. 1. Provinces in Iran in which incidence and prevalence of multiple sclerosis have been studied.
2. Methods 2.1. Patient selection This study was conducted in the Sistan & Balouchestan province, which is the largest province of Iran, bordering Afghanistan and Pakistan (Fig. 1). It is located in southeastern Iran (29◦ N and 60◦ E), and has the highest birth rate in the country (over 3%), with a population of over 2.5 million and a high proportion of young adults (45.7%), aged between 16 and 50. The population consists of two ethnic “Fars” groups, who live mainly in the northern part of the province and the “Balouches”, residing mainly in the southern part. The province is in the subtropical/tropical region with dry and hot weather in summer and dry-cold weather in winter. The study population includes all residents living in this area since the past 15 years, except for Afghan refugees. The socioeconomic status of the inhabitants is more or less similar to that of other parts of the country. Health services are provided by private, governmental and academic faculty neurologists affiliated to teaching hospitals. Because of the high prices of different drugs, especially interferons, prescribed as first line of treatment for MS, all cases are referred to our university hospital for confirmation of diagnosis, following which the patient, once reassured, can begin the treatment prescribed. All data had been archived, therefore gathering it was easy for us, except for those patients who had a diagnosis confirmed elsewhere in the country or had migrated to this province for different reasons. The authors conducted a cross-sectional case register study from January to August 2010. The diagnosis was based on clinical findings, brain and spinal cord MRI studies, CSF analyses and visual evoked potential (VEP), according to the McDonald criteria and its revision [13,14]. We tested all patients for collagen-vascular
diseases and had antinuclear antibody (ANA), ds-DNA and antiphospholipid antibody laboratory tests done. Routine laboratory examinations, visual evoked potential, and CSF analyses were performed and brain and cervical cord MRIs were taken in almost all patients; some did not give us consent to perform a lumbar puncture and hence CSF analyses were not carried out for these patients. All cases with clinically definite MS, Clinically Isolated Syndrome (CIS) and Neuromyelitis Optica (NMO; Devic’s disease) were enrolled for the study. The diagnosis of NMO was based on the medical history of patients (development of optic neuritis and presence of extensive demyelinating lesions in the cervical spinal cord as well as the results of visual evoked potential. We could not measure aquaporin-4 antibody in the CSF in our lab. Using our database, we could trace patients who had left the province or had died and therefore we included them in the study to calculate the actual incidence rate if they were born in this region or had lived there since the past 10 years; however they were excluded for calculation of the prevalence rate. We had also excluded patients who had recently moved to the province for various reasons. Since MS affects people, aged 16–50 years, we also intended to find the incidence and prevalence for this age range. Finally we calculated prevalence during the study years in the total population and its subcategories according to their age range and gender. We did not have any patient in whom the disease had begun after the age of 50. Demographic information, including name, parents’ name, age, marital status, and education were obtained from the patients or their relatives. We also collected other relevant clinical data, such as the first neurological episode compatible with MS disease (type and year), CSF and MRI findings, occupation and place of birth and residence The Iranian Bureau of Statistics regularly estimates the average annual population, based on the 1996 and 2006 census data. To calculate the prevalence and incidence, we used the above
306
A. Moghtaderi et al. / Clinical Neurology and Neurosurgery 115 (2013) 304–308
mentioned data to find the population at risk (denominator). This study was approved by the Institutional Ethics Committee of the Zahedan University of Medical Sciences. 2.2. Statistical analysis MS prevalence and incidence rates per 100,000 persons were calculated according to gender and age groups between the years 2006 and 2009. We used SPSS software for Windows, Version 15 (SPSS Inc., Chicago, IL, USA) to calculate median, arithmetic mean, and standard deviation for different variables. Comparisons were accepted as statistically significant at the conventional p-value of less than 0.05. Fig. 2. Number of new cases of multiple sclerosis during the last 10 years.
3. Results After exclusion of 31 patients from the study group, a total of 206 patients were identified during the last 15 years according to the McDonald criteria. In 2009, 188 patients were aged between 16 and 50 years and 36 patients were new cases. The total population at risk (aged 16–50 years) in the same year was 1,346,367 persons in the province. Therefore, in the year 2009, prevalence and incidence rates were 13.96 and 2.67 per 100,000 persons; corresponding values for the last three years are presented in Table 1. Table 2 shows the incidence and prevalence of MS diseases, according to the age range and sex, in the population at risk. Based on these values, female to male ratios were between 2.22 (in 2006) and 2.18 (in 2009). In the above mentioned years the incidence rates increased 2.4 and 2.7 times in women and men, respectively. Table 3 shows total prevalence rate according to sex. Overall prevalence and incidence rates increased about 1.5 and 2.4 times in women and 1.52 and 2.7 times in men, respectively. In 2009, 18 patients (8.73%) were under 16 or over 51 years old, most being between 16 and 35. In 2009, the prevalence rate in the <15, 16–35, 36–50 and ≥51-year age groups were 1.44, 14.34, 12.24 and 1.45 per 100,000 persons, respectively. Total incidence rates were 0.59, 0.84, 1.11 and 1.47 per 100,000 people in the years 2006–2009, respectively, while the total prevalence rates in these years were 5.14, 5.75, 6.58 and 7.69 per 100,000 individuals, respectively (Table 4). Mean ages for the first symptom were 28.2 ± 9.8 and 26.5 ± 8.2 years for men and women, respectively. Mean time for the diagnosis after the first presentation was 1.7 ± 1.1 years. The relapsing-remitting type of the MS was the most prevalent form
(65.8%), followed by the secondary progressive (20%), primary progressive (6.7%) and the progressive-relapsing (2%) types. Eight cases (5.4%) had Devic’s disease. Mean scores for EDSS scores for men and women were 3.62 ± 2.3 and 2.70 ± 2.1, respectively; this mean score for patients, aged between 16 and 35 years, was 2.82 ± 2.3 and for patients aged 36–50 years was 3.42 ± 2.9. Numbness and other sensory disturbances, except for visual loss, were the most frequent presenting manifestations (39.8%) followed by motor dysfunction (28.6%) and optic neuritis (28.2%). Twenty-two percent of the cases had more than one symptom at the first presentation. Thirteen cases (6.2%) had positive family history in their first-degree relatives and one couple had conjugal MS, indicating that the husband had been affected by the disease after marriage. Eighty-six percent of subjects were married and only 29% were of Balouch origin. Fig. 2 shows the increasing number of the new cases during the last ten years. 4. Discussion We found age-adjusted and total prevalence rates of 13.96 and 7.69 per 100,000 persons in southeastern Iran in 2009. The incidence rate is increasing rapidly, being 3.62 for women, 1.75 for men and 2.67 per 100,000 persons totally in the last year of the study. Located in a tropical/subtropical region, this province of Iran can be classified as an intermediate area for MS prevalence. To the best of our knowledge this is the first age-adjusted report of the incidence rate of MS in an Iranian population.
Table 1 Age-adjusted prevalence and incidence of MS during 2006–2009 in Sistan & Balouchestan province, Iran.
2006 2007 2008 2009
Population at risk (16–50 years)
Total MS patients
New MS patients
Prevalence per 100,000 persons
Incidence per 100,000 persons
1,215,874 1,259,281 1,302,096 1,346,367
113 129 154 188
13 19 26 36
9.29 10.24 11.82 13.96
1.07 1.50 1.99 2.67
Table 2 Age-adjusted prevalence and incidence of MS during 2006–2009 according to sex in Sistan & Balouchestan province, Iran. Population at risk
2006 2007 2008 2009
Women (16–50 years)
Men (16–50 years)
599,559 619,944 641,021 662,816
616,314 639,336 661,074 683,551
Total MS patients (F/M)
New MS patients (F/M)
Prevalence per 100,000 persons (F/M)
Incidence per 100,000 persons (F/M)
78/35 89/40 106/48 129/59
9/4 13/6 17/9 24/12
13.00/5.67 14.35/6.25 16.53/7.26 19.46/8.63
1.50/0.64 2.09/0.94 2.65/1.36 3.62/1.75
A. Moghtaderi et al. / Clinical Neurology and Neurosurgery 115 (2013) 304–308
307
Table 3 Total prevalence and incidence of MS for all ages during 2006–2009 according to sex in Sistan & Balouchestan province, Iran. Population at risk
2006 2007 2008 2009
Women
Men
1,178,813 1,218,999 1,260,335 1,303,185
1,226,928 1,268,643 1,311,777 1,356,376
Total MS patients (F/M)
New MS patients (F/M)
Prevalence persons (F/M)
Incidence persons (F/M)
84/39 97/45 114/56 138/68
9/4 13/6 17/9 24/12
7.13/3.18 7.95/3.54 9.05/4.27 10.59/5.01
0.76/0.32 1.06/0.47 1.35/0.68 1.84/0.88
Table 4 Total prevalence and incidence of MS during 2006–2009 in Sistan & Balouchestan province, Iran.
2006 2007 2008 2009
Total population
Total MS patients
Total prevalence per 100,000 persons
Total incidence per 100,000 persons
2,198,443 2,243,478 2,340,425 2,444,733
113 129 154 188
5.14 5.75 6.58 7.69
0.59 0.84 1.11 1.47
Little is known about the epidemiology of MS in Iran. Wadia and Bhati in 1990 found an intermediate prevalence of MS among the Iranian immigrant (Zoroastrians) in India during the 7th and 10th centuries AD; the age-adjusted prevalence in Bombay was 24/100,000 and it was higher than the usual low risk populations of Asian and African countries [15]. Two years earlier, in a door to door survey conducted among Iranian immigrants (Parsis) living in colonies in Bombay, the prevalence rate of clinically definite MS was reported to be 21/100,000 [16]. Ale-Yasin and his colleagues [9] have reported the demographic and clinical characteristics of 318 patients living in Tehran, Iran; although the study was not population based, they estimated a prevalence of 4/100,000. In their study, sensory impairment was the most frequent presenting symptom, followed by visual impairment. The true frequency of optic neuritis and any case of Devic’s disease have not been reported. In another six-month study, published in a local Persian journal the point prevalence rate among MS patients living in northern Iran (Mazandaran) had been reported to be 20.1/100,000 [17]; the study was not population-based and 582 MS patients from one registry were used to calculate the prevalence rate; the female to male ratio was 2.6 and the most frequent reported symptom was visual disturbances. The only report from the southwestern province of Iran (Khuzestan) showed a crude prevalence rate of 14.04/100,000 [11]; in this study the prevalence rate for a resident Arab population was much lower compared to the inhabitants of Persian origin (8.58 vs. 16.16/100,000). According to the high rate of NMO in our patients it seems that the “Asian type” of MS with optico-spinal involvement, transverse myelitis and severe visual loss is more common in this area. However this needs to be further investigated with more cases. The first Iranian population-based study was done in central province of Isfahan which revealed a prevalence rate of 35.5/100,000 in 2005 [12]. The same center reported a crude prevalence rate of 43.8/100,000 for a total patient population of 1718 after one year [18]. In this study the prevalence rate in women was 3.4 times more than that of men (69.6 vs. 19.2). There are probably some reasons that the reported prevalence rate was higher than other parts of the country; however, no one has yet looked at the more important question that not all the reported patients were visited by the researchers and most of them were enrolled into the study based on the discharge letter issued by neurologists. Sometimes it is difficult to differentiate between MS and disseminated encephalomyelitis (DEM) because McDonald diagnostic criteria are purely quantitative and lack any qualitative descriptive features.
The appearance of plaques is more important than their number to differentiate MS from recurrent DEM [8]; this may increase the rate of misdiagnosis based on the McDonald criteria. Prevalence studies have traditionally focused on a geographical area and population group. It seems logical that the researcher counts only patients whose disease started after they had been living for a longtime in the region, otherwise it may show an abnormally high prevalence rate [19]. Isfahan is the second largest city of Iran. Due to its location in the central part of country, many people from most parts of Iran move there, living with their families, in search of jobs, and to have access to sophisticated medical facilities: due to the chronicity of multiple sclerosis and the constant need for treatment and access to an expert neurologist, they may remain in the city for a long time. It was not reported whether those patients who belonged to immigrated population had been excluded from the study or not. Therefore, the population at risk (denominator) is fixed but the number of patients increased. We suppose that this is the most important reason for the high prevalence rate reported in central parts of Iran. However, based on the theory that MS may be caused by an infection, the high number of patients may be due to an epidemic infection during the last 20 years, which has now presented itself as clinical neurologic multiple sclerosis (CNMS) [1,7,20]. Confirming or refuting these theories needs more accurate studies. In a newly published article, Elhami et al. [21] reported that the MS incidence in 2008 was 2.93/100,000 population in Tehran, Iran. Middle-Eastern countries located in Asia and a part of Africa are classified as the low risk areas [22,23] but other studies revealed that the worldwide prevalence of MS is much higher than those previously reported [24]. It seems that the distribution of MS is very uneven due to great differences among regions in the same latitude and different parts of the same countries [25]. In Kuwait the reported crude prevalence has increased from 10/100,000 in 1980 [26] to 14.7/100,000 in 2000 [27]. The prevalence among a pure Kuwaitis population was 11.02/100,000 in 1993 and increased to 31.15/100,000 in 2000 [28]. The reported prevalence in Jordan was 7/100,000 [29] but recently it has been reported to be 32/100,000 in one study [30] and 39 per 100,000 in another [31]. In Saudi Arabia, the prevalence rate of MS increased from 8/100,000 in 1977 [32] to 25/100,000 in 1998 [33]. However, we cannot draw a definite conclusion about the prevalence of MS in Middle-Eastern countries due to methodological inconsistencies among published studies. Nevertheless, we can conclude that the prevalence in those countries is escalating, and it depends on the specific population and environment of the study [28].
308
A. Moghtaderi et al. / Clinical Neurology and Neurosurgery 115 (2013) 304–308
Our study has some limitations which may to a slight extent affect the calculation of incidence and prevalence of the disease. Despite the fact that the authors have tried to collect complete data from all patients, there were some who had moved to other major central cities, seeking better health care, affecting possibly the true incidence and prevalence of the disease. It needs to be mentioned that a meticulous door-to-door study would show higher number of patients in this area, but because of population dispersion in an extensive area, such a study is very difficult and virtually impossible. Although our study does report figures regarding MS prevalence, further studies are needed to answer critical questions regarding factors that impact MS prevalence. Based on their findings, the authors conclude that the prevalence of MS in southeastern Iran is in the intermediate range in the population at risk, and that the incidence rate is growing faster than previous years. More follow up studies are needed to understand and analyze the patterns of the disease in this region. Acknowledgements This paper was based on the MD thesis of Dr. F. Rakhshanizadeh and was supported financially by the Dean for Research Affairs at the Zahedan University of Medical Sciences. The authors would like to acknowledge Ms. Nilufar Shiva and Dr. Mohsen Javadzadeh for language editing of the manuscript. References [1] Kurtzke JF. Epidemiologic evidence for multiple sclerosis as an infection. Clinical Microbiology Reviews 1993;6(October (4)):382–427. [2] Turk Boru U, Alp R, Sur H, Gul L. Prevalence of multiple sclerosis door-to-door survey in Maltepe, Istanbul, Turkey. Neuroepidemiology 2006;27(1):17–21. [3] Kurtzke JF. Epidemiology of multiple sclerosis. Does this really point toward an etiology? Lectio Doctoralis. Neurological Sciences 2000;21(December (6)):383–403. [4] Kurtzke JF. Epidemiology and multiple sclerosis. Revista de Neurologia 2002;35(December (12)):1177. [5] Kurtzke JF. A reassessment of the distribution of multiple sclerosis. Part one. Acta Neurologica Scandinavica 1975;51(February (2)):110–36. [6] Poser CM. Notes on the epidemiology of multiple sclerosis. Journal of the Formosan Medical Association 1995;94(June (6)):300–8. [7] Kurtzke JF. Epidemiology and etiology of multiple sclerosis. Physical Medicine and Rehabilitation Clinics of North America 2005;16(May (2)):327–49. [8] Poser CM, Brinar VV. The accuracy of prevalence rates of multiple sclerosis: a critical review. Neuroepidemiology 2007;29(3–4):150–5. [9] Ale-Yasin H, Sarai A, Alaeddini F, Ansarian E, Lotfi J, Sanati MH. Multiple slerosis: a study of 318 cases. Archives of Internal Medicine 2002;5(1):24–7. [10] Ghandehari K, Riasi HR, Nourian A, Boroumand AR. Prevalence of multiple sclerosis in north east of Iran. Multiple Sclerosis 2010;16(December (12)):1525–6. [11] Sharaffadinzadeh N, Majdinasab N, Kashipazha D, Shalbafan B. Multiple sclerosis in Khuzestan, Iran. In: Sixth international Iranian congress on MS. Tabriz, Iran: Tabriz Neuroscience Research Center; 2009. p. 9.
[12] Etemadifar M, Janghorbani M, Shaygannejad V, Ashtari F. Prevalence of multiple sclerosis in Isfahan, Iran. Neuroepidemiology 2006;27(1):39–44. [13] McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD, et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Annals of Neurology 2001;50(July (1)):121–7. [14] Polman CH, Reingold SC, Edan G, Filippi M, Hartung HP, Kappos L, et al. Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald Criteria”. Annals of Neurology 2005;58(December (6)):840–6. [15] Wadia NH, Bhatia K. Multiple sclerosis is prevalent in the Zoroastrians (Parsis) of India. Annals of Neurology 1990;28(August (2)):177–9. [16] Bharucha NE, Bharucha EP, Wadia NH, Singhal BS, Bharucha AE, Bhise AV, et al. Prevalence of multiple sclerosis in the Parsis of Bombay. Neurology 1988;38(May (5)):727–9. [17] Abedini M, Habibi-Saravi R, Zarvani A, Farahmand M. Epidemiology of multiple sclerosis in Mazandran province in 2007. Journal of Mazandaran University of Medical Sciences 2008;18(66):82–7 (Persian). [18] Saadatnia M, Etemadifar M, Maghzi AH. Multiple sclerosis in Isfahan, Iran. International Review of Neurobiology 2007;78(4):357–75. [19] Mayr WT, Pittock SJ, McClelland RL, Jorgensen NW, Noseworthy JH, Rodriguez M. Incidence and prevalence of multiple sclerosis in Olmsted County, Minnesota, 1985–2000. Neurology 2003;61(November (10)):1373–7. [20] Kurtzke JF, Hyllested K. Multiple sclerosis in the Faroe Islands and the lack of protection by exposure in infancy. Neuroepidemiology 1992;11(2):90–9. [21] Elhami SR, Mohammad K, Sahraian MA, Eftekhar H. A 20-year incidence trend (1989–2008) and point prevalence (March 20, 2009) of multiple sclerosis in Tehran, Iran: a population-based study. Neuroepidemiology 2011;36(3):141–7. [22] Kurtzke JF. Epidemiologic contributions to multiple sclerosis: an overview. Neurology 1980;30(July (7 Pt 2)):61–79. [23] Poser CM. The epidemiology of multiple sclerosis: a general overview. Annals of Neurology 1994;36(December (Suppl. 2)):S180–93. [24] Rosati G. Descriptive epidemiology of multiple sclerosis in Europe in the 1980s: a critical overview. Annals of Neurology 1994;36(December (Suppl. 2)):S164–74. [25] Rosati G. The prevalence of multiple sclerosis in the world: an update. Neurological Sciences 2001;22(April (2)):117–39. [26] Al-Din AS, Khogali M, Poser CM, Al-Nassar KE, Shakir R, Hussain J, et al. Epidemiology of multiple sclerosis in Arabs in Kuwait: a comparative study between Kuwaitis and Palestinians. Journal of the Neurological Sciences 1990;100(December (1–2)):137–41. [27] Alshubaili AF, Alramzy K, Ayyad YM, Gerish Y. Epidemiology of multiple sclerosis in Kuwait: new trends in incidence and prevalence. European Neurology 2005;53(3):125–31. [28] Al-Hashel J, Besterman AD, Wolfson C. The prevalence of multiple sclerosis in the Middle East. Neuroepidemiology 2008;31(2):129–37. [29] Kurdi A, Ayesh I, Abdallat A, Maayta U. Different B lymphocyte alloantigens associated with multiple sclerosis in Arabs and North Europeans. Lancet 1977;1(May (8022)):1123–5. [30] Al-Din AS, El-Khateeb M, Kurdi A, Mubaidin A, Wriekat A, Al-Shehab A, et al. Multiple sclerosis in Arabs in Jordan. Journal of the Neurological Sciences 1995;131(August (2)):144–9. [31] El-Salem K, Al-Shimmery E, Horany K, Al-Refai A, Al-Hayk K, Khader Y. Multiple sclerosis in Jordan: a clinical and epidemiological study. Journal of Neurology 2006;253(September (9)):1210–6. [32] Yaqub BA, Daif AK. Multiple sclerosis in Saudi Arabia. Neurology 1988;38(April (4)):621–3. [33] Daif AK, Al-Rajeh S, Awada A, Al Bunyan M, Ogunniyi A, AbdulJabar M, et al. Pattern of presentation of multiple sclerosis in Saudi Arabia: analysis based on clinical and paraclinical features. European Neurology 1998;39(3):182–6.