PREVALENCE OF MULTIPLE SCLEROSIS IN SAUDI ARABIA

Maryam Alshanqiti 1 , Fawaz Fahad Alotaibi 2 , Jafer Mohammed Alahmed 3 , Marwah Lafi Alrehaili 1 , Salwa Saleem Alalwi 1 and Dr. Farah Mansuri 4 . 1. Medical intern, Taibah University, Medina, Saudi Arabia. 2. Medical intern, Majmaah University, Majmaah, Saudi Arabia. 3. Medical intern, Jilin University, Changchun, China. 4. MBBS, MCPS, FCPS, Professor Dept of Community & Family Medicine, Taibah University, Al Medinah Munawara. ...................................................................................................................... Manuscript Info Abstract ......................... ........................................................................ Manuscript History


Introduction:-
Multiple sclerosis (MS) is a neurological disorder that typically affects adults in their reproductive years mostly between 20 and 40 causing major disability 1 .Clinically there are no specific signs,but some feature are highly suggestive of MS such as relapsing an remitting course, optic neuritis, lhermitte sign, internuclearophthalmoplegia, fatigue and heat sensitivity (Uhthoff phenomenon). Symptoms varies including sensory deficits in the limbs or one side of the face, visual loss, acute or subacute motor weakness, diplopia, gait disturbance and balance problems, , vertigo, bladder problems, limb ataxia, acute transverse myelitis, and pain. The onset is often polysymptomatic. The most common presenting symptoms are sensory disturbances, then weakness and visual disturbances 2 .
On the other hand, a study done in the the Lazio region, Italy the overall prevalence rate standardized to the European Standard Population was 119.6/100,000 (95 % CI 116.8-122.4)1. In Leeds, UK, crude prevalence of MS in all ages was 97 per 100,000 3 . A study conducted in Santaréma district in the center of Portugal the crude prevalence rate found was 46.3/100,000. According to a Canadian study conducted through tow decades the province of British Columbia founded to have a prevalence rate that is among the highest globally 5 .
In a cohort study conducted to estimate the mortality rate using prospectively collected data from the UK General Practice Research Database (GPRD) of the 1,822 MS cases, 130 (7.1 %) died during 14,295 person-years of followup, while 573 (3.1 %) referents died during 144,760 person-years of follow-up. The crude death rate for MS patients was 9.1 (95 % CI 7.6-10.8) per 1,000 person-years compared with 4.0 (95 % CI 3.6-4.3) per 1,000 person-years for 1583 the non-MS counterparts. Mortality rates were higher in MS patients compared with their matched controls in each age group and for both males and females 6 .
In Saudi Arabia as such population based evidence on prevalence of MS is not available. However the pervasiveness of MS in Saudis estimated to be approximately 40/100,000 in 2008. Though MS found to be rare in Saudis, it is currently clear that it is predominant, under-diagnosed and expanding we aim in this study to estimate the prevalence of multiple sclerosis among Saudi citizens 3 .

Methodology:-
A cross sectional study was done to estimate the prevalence of multiple sclerosis in KSA during June-July 2016. A total of 633 participants were included from various areas of the Kingdom of Saudi Arabia to respond to this selfadministered online questionnaire. The sample comprised of 202(31.9%) male, and 431(68.1%) females.  (20)(21)(22)(23)(24), While (34.1%) of the respondents Aged between (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35), While (18.8%) of the respondents Aged more than 35.            It's evident from table (12) that (3.4%) of the respondents suffer from anemia, and (8.0%) of the respondents suffer from broncheal asthma, while (1.1%) of the respondents suffer from color blindness, and (18.2%) of the respondents suffer from diabetes, also (11.4%) of the respondents suffer from eczema, and (1.1%) of the respondents suffer from eye allergy, as (10.2%) of the respondents suffer from G6PD anemia, and (1.1%) of the respondents suffer from gout, while (2.3%) of the respondents suffer from hair falling.     (15)    It's evident from table (17) that (3.8%) of the respondents who suffer from MS also suffer from Genetic disease, while (96.2%) of the respondents who suffer from MS don't suffer from Genetic disease. Also (50%) of the respondents who suffer from MS and Genetics disease suffer from diabetes, and (50%) of the respondents who suffer from MS and Genetics disease suffer from hypertension. -There are statistically significant differences at the level of significance (P <0.05), in the prevalence of MS according to the variable of "age" ( X    1594 Table (

Discussion:
The prevalence of MS as reported in our study was 11% and this is much higher than expected for a middle eastern population. The findings in our study were 28.3% of males as compared to 71.6 % females had MS as picked up in this online survey. Prevalence in our study is astonishingly high. The incidence of 8.5/100 000 inhabitants during 2003-2007 was reported on MS frequency in the southern 7 and eastern 8 parts of Norway which is considered as a high risk area of MS. Similarly an Iranin study reports MS incidence as 0.68 to 9.1/100,000 per year in the Iranian population and Prevalence was reported in all studies and ranged from 5.3 to 74.28/100,000 with the higher prevalence among females (female/male ratio ranged from 1.8 to 3.6).
While in Kuwait during 2013, POMS incidence rate and prevalence(per 100,000) were 2.1 and 6.0 respectively. increased 10-fold from 20/100 000 in 1963 to 211 (95% CI 198.3 to 224.2) per 100 000 in 2013. The prevalence rate of 211/100 000 inhabitants was higher than a recent prevalence report of 186/100 000 in Western Norway. 9 These diverging results are most likely a result of the limitation of using data from the National Patients Registry included in this recent nationwide study. 9 Previous Norwegian studies using hospital records (as in our study) have reported MS prevalence rates of 170/100 000 in the south-eastern county of Oslo, 10 180/100 000 in the southern county of Vest-Agder 7 and 185.6/100 000 in the eastern county of Oppland. 8 The prevalence rate in Hordaland was, thus, similar to the latest report from the UK, 11 but higher than reported in Denmark, 12 Sweden 13 and South East Wales, 14 and lower than reports from Orkney, Shetland and Aberdeen City, 15  1597 sample collection termination day, in order to calculate the valid prevalence. Thus, the follow-up identified undiagnosed patients who had symptom onset prior to 1 January 2003 and illustrates that the prevalence is rising and most interestingly, that the date for study termination has a major impact on prevalence. The rise in prevalence is a consequence of the underestimated prevalence reported previously 16 due to the time delay between onset and diagnosis. However, the time delay between onset and diagnosis is decreasing and consequently, the methodological issue of underestimated prevalence will probably be reduced in future studies. The incidence of MS in Hordaland County has in previous studies increased from 0.2/100 000 in 1935, 17 to 0.67/100 000 in 1951 18 and to 4.7/100 000 in 1978-1982. 19 However, in the present long-term follow-up study, we also identified patients with disease onset years prior and thus higher incidence rates of 1.8/100 000 during 1953-1957, 6.9/100 000 during 1978-1982 followed by a stable high level of approximately 7-8/100 000 during later years. Thus, this tendency towards increase in incidence rates and prevalence rates of MS, presented in the repeated studies we provide in this paper, demonstrates the necessity of repeated surveillance to study valid time trends of MS incidence rates. 20 . 9 We showed relatively stable incidence rates during the past three decades. However, since we reported the year-ofonset incidence, we observed a drop in rate probably due to delayed diagnosed cases for the latest 5-year period. The stable incidence rate was consistent with reports from Olmstead County, Minnesota, USA, 21 andCanada, 22 but was in contrast to a downward incidence trend in the Orkney Islands, 23 the Faroe Islands 24 and in Gothenburg, 25 and the increased incidence trends in Denmark, 20 South East-Wales, 14 NortheastIreland 25 and another Canadian population. 27 The rise in prevalence of MS could partly be explained by the historical large increase in incidence of the disease until 1978-1982. The early increase in prevalence might be explained by the increase in incidence the first 3-4 decades. Also, owing to the onset of disease approach to incidence and prevalence estimations, and the time delay between onset and diagnosis, the prevalence has a delay up to about mean 7-9 years until the 1990's and hence, increase in incidence is followed by a parallel increase in prevalence after almost a decade. Because of the retrospective year of onset approach to incidence, the prevalence is catching up later. However, the continued recent increase in prevalence was not associated with a parallel increase in incidence. Thus some of the increase in prevalence in recent years may be explained by improved diagnostics especially with the introduction of MRI in the 1990s and the ability to identify younger patients and more benign disease living longer with the disease. The diagnostic criteria which has evolved from the early clinically based criteria 28 to MRI-grounded criteria, 29 recently revised, 30 have improved case ascertainment throughout the study period. Systematic use of the revised diagnostic criteria of McDonald with frequent use of repeated MRIs may lead to an increased diagnosis of patients with vague symptoms due to a benign disease. However, the diagnosing of more benign cases had probably a limited impact on prevalence, leaving increased survival as the most likely explanation to our findings. Improved survival in MS, possible due to more frequent use of advanced disease-modifying therapies, 31 was probably the most important factor related to the observed increase in prevalence. The importance of improved survival on the observed increase in prevalence was also supported by the shift towards an older age distribution of the present 2013 prevalence cohort compared with the prevalence reported in the 2003 study. 16 A change in age distribution has also previously been reported from Canada and the UK. 11 22 Given the stable incidence rate, the higher ages in the cohort probably relate to improved survival either due to disease-modifying therapies or attributed to a general increase in life expectancy during the last decades. To determine the impact of treatment on survival, standardized mortality ratio calculations comparing MS to the general population in Norway are needed. 32 In contrast to several reports of increasing female to male ratios in MS 14 33 34 the overall rate has been stable in Hordaland County throughout the past six decades. Our follow-up data showed a stable sex-ratio throughout the period and does not indicate gender-specific environmental risk factors which affect women more than men.
Explaining the stable incidence rates by changes in environmental risk factors for MS seems challenging. Epstein-Barr virus 35 infections are stable, but cigarette smoking 36 has declined during the last decadesand may have reduced the risk of MS. However, both consumption of dietary salt intake 37 through processed food and use of sun-protection products, 38 which may lead to reduced serum levels of vitamin D 39 has increased in the past three decades. These may be two other factors associated with increased risk of MS.. Improved case ascertainment during the past six decades can probably explain some of the increased prevalence found in the present study. This was indicated by the steady decline in time delay between onset and diagnosis of MS. Revised diagnostic criteria, 30 focusing on active use of MRI to define disseminated disease in time and space, 1598 combined with improved disease-modifying treatments has increased the diagnostic awareness among physicians and patients, and have therefore, important impact on this time-delay.
Our study provides comprehensive data on MS prevalence and incidence during 60 years and confirms Norway as a high risk area for MS. The steady increase in MS incidence from the 1950s followed by a stable high incidence during the past three decades, calls for further studies focusing on environmental factors to explain this pattern. The tendency to identify more MS cases at follow-up, demonstrated in this study, indicates that previous studies with data collection close to the prevalence day might have underestimated the prevalence of MS. Thus future studies on prevalence of MS should explore the occurrence of disease with a prolonged follow-up of several years after prevalence day in order to estimate the true prevalence of disease.

Conclusion
As shown above that most of the respondents (68.1%)were female, Also most of them (47.1%) aged between (20)(21)(22)(23)(24)  The analysis illustrated that (64.2%) of the respondents who suffer from MS don't have relatives suffer from MS, and (33.3 %) of the respondents who suffer from MS who have relatives suffer from MS have a mother suffers from MS, also (5.7%) of the respondents who suffer from MS have a symptom of Weakness in arm or leg, Numbness in the extremities, Loss of Balance or Fatigue Exhaustion, while (83.0%) of the respondents who suffer from MS don't suffer from immune diseases, and (22.2 %) of the respondents who suffer from MS and immune diseases suffer from rhumatic fever or erthymatosis, as (96.2%) of the respondents who suffer from MS don't suffer from Genetic disease, and (50%) of the respondents who suffer from MS and Genetics disease suffer from diabetes or hypertension.
The results of analysis illustrated that there were statistically significant differences between those with and without MS as regard to age, nationality and the region (P<0.05), while there were no statistically significant differences as regard to gender, education and marital status(P>0.05). Also, MS was more prevalent between 25 and 30 years (49.1%), in Saudi nation (84.9%) and the central region (39.6%).
Also, there were statistically significant differences at the level of significance (P <0.05), in the prevalence of MS in the relatives of the patients with and without MS in favor of no prevalence of MS in the relatives of (64.1%) patients with and without of respondents, We found that there were statistically significant differences between those with and without MS as regard to absence of suspicious symptoms of MS of Weakness in arm or leg, Loss of Balance and Anxiety (P<0.05), while there were no statistically significant differences as regard to Numbness in the extremities, Muscles Cramps, Walking Difficulty, Fatigue Exhaustion, Vertigo, Headache, Convulsion(Epilepsy), Vision Problems, Bladder Problems, Intestinal Problems, Sexual Problems, Depression and Memory and Thinking Problems (P>0.05).as most of the respondents stated the absence of Weakness in arm or leg (99.5%), Loss of Balance (99.5%) and Anxiety (99.8%).

1599
Finally, we indicated that there were statistically significant differences between those with and without MS as regard to absence of immune diseases and Genetics diseases (P<0.05), as (97.6%) of the respondents reported absence of immune diseases and (96.2%) of the respondents reported absence of Genetics diseases.

Recommendations for patients:
Patients have to Learn as much as possible about their disease which in this case is MS, also they have to make sure that their diagnosis with MS is definitive, and to understand that the symptoms of MS can not be predicted, and they shouldn't delay treatment as well as avoiding triggers that relapses MS, finally, they have to never give up hope even if there are currently no cure of MS, but the future is promising of discovering a cure soon.

Recommendations for physicians:
Physicians should first make sure that the diagnosis with MS is definitive, and they have to guide patients with the best practices for the alleviation of MS, also Physicians should start with prescribing medicines to modify the course of MS, then Physicians should prescribe medicines to control the effects of MS, also during the trip of treating MS, Physicians should bring hope in the hearts of patients so as not to suffer despair and frustration.

Recommendations for future research:
We recommend that future studies focus on escalating secondary multiple sclerosis and escalating Relapser multiple sclerosis. Also, future research could state the best practices of managing multiple sclerosis by patients at home and by Physicians clinically. And future research could illustrate the recent alternative treatments of MS.